LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

PubMed

Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

2009-05-01

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

2017-11-01

The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

DTIC Science & Technology

2014-10-01

Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer PRINCIPAL INVESTIGATOR: Elizabeth A. Platz CONTRACTING...Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0545 5c...combination of telomere length variability in prostate cancer cells and short telomere length in cancer-associated stromal cells is an independent

Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study.

PubMed

Varshney, Anshul; Gupta, Rohit; Verma, Sanjiv K; Ahmad, Sohaib

2017-07-01

Prognostic markers of acute liver failure (ALF) are based on clinical, laboratory or radiological parameters. Most of the biochemical markers are based on hepatic degeneration. We studied the impact of serial serum alpha-fetoprotein (AFP) levels, a marker of liver regeneration, on the outcome of the patients with ALF. AFP levels were estimated on days 1 and 3 of hospitalisation of 32 patients with ALF and the ratio (AFP day3/day1) was calculated. All subjects were categorised as group A (expired) or group B (survived). The AFP ratio was 0.84  +  0.15 in group A (n = 20) versus 1.55  +  0.70 in group B (n = 10); P < 0.001. However, the absolute initial AFP values were not associated with the outcome, favourable or unfavourable. We conclude that AFP levels change dynamically during ALF and have the potential to be used as a predictor of outcome in isolation or in combination with well-established prognostic markers.

Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets.

PubMed

Hadler-Olsen, Elin; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-08-01

Biomarkers are used as tools in cancer diagnostics and in treatment stratification. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs). This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. It has therefore been expected that MMPs could serve as both diagnostic and prognostic markers in cancer patients, but despite a huge number of studies, it has been difficult to establish MMPs as cancer biomarkers. In the present paper, we assess some of the challenges associated with MMP research as well as putative reasons for the conflicting data on the value of these enzymes as diagnostic and prognostic markers in cancer patients. We also review the prognostic value of a number of MMPs in patients with lung, colorectal, breast, and prostate cancers. The review also discusses MMPs as potential target molecules for therapeutic agents and new strategies for development of such drugs.

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC

PubMed Central

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-01-01

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. Conclusion eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy. PMID:28060762

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

PubMed

Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-02-14

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

Prognostic relevance of Centromere protein H expression in esophageal carcinoma.

PubMed

Guo, Xian-Zhi; Zhang, Ge; Wang, Jun-Ye; Liu, Wan-Li; Wang, Fang; Dong, Ju-Qin; Xu, Li-Hua; Cao, Jing-Yan; Song, Li-Bing; Zeng, Mu-Sheng

2008-08-13

Many kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features. We examined the expression of CENP-H in immortalized esophageal epithelial cells as well as in esophageal carcinoma cells, and in 12 cases of esophageal carcinoma tissues and the paired normal esophageal tissues by RT-PCR and Western blot analysis. In addition, we analyzed CENP-H protein expression in 177 clinicopathologically characterized esophageal carcinoma cases by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. The level of CENP-H mRNA and protein were higher in the immortalized cells, cancer cell lines and most cancer tissues than in normal control tissues. Immunohistochemistry showed that CENP-H was expressed in 127 of 171 ESCC cases (74.3%) and in 3 of 6 esophageal adenocarcinoma cases (50%). Statistical analysis of ESCC cases showed that there was a significant difference of CENP-H expression in patients categorized according to gender (P = 0.013), stage (P = 0.023) and T classification (P = 0.019). Patients with lower CENP-H expression had longer overall survival time than those with higher CENP-H expression. Multivariate analysis suggested that CENP-H expression was an independent prognostic marker for esophageal carcinoma patients. A prognostic value of CENP-H was also found in the subgroup of T3 approximately T4 and N0 tumor classification. Our results suggest that CENP-H protein is a valuable marker of esophageal carcinoma progression. CENP-H might be used as a valuable prognostic marker for esophageal carcinoma patients.

Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

PubMed

Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

2016-04-01

The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

PubMed

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.

PubMed

Gessner, C; Woischwill, C; Schumacher, A; Liebers, U; Kuhn, H; Stiehl, P; Jürchott, K; Royer, H D; Witt, C; Wolff, G

2004-01-01

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia.

PubMed

Eberhart, Charles G; Kratz, John; Wang, Yunyue; Summers, Krista; Stearns, Duncan; Cohen, Kenneth; Dang, Chi V; Burger, Peter C

2004-05-01

Several molecular and histopathological prognostic markers have been proposed for the therapeutic stratification of medulloblastoma patients. Amplification of the c-myc oncogene, elevated levels of c-myc mRNA, or tumor anaplasia have been associated with worse clinical outcomes. In contrast, high TrkC mRNA expression generally presages longer survival. The goal of this study was to evaluate the prognostic value of c-myc, N-myc and TrkC expression in medulloblastomas and compare them to histopathological classification. We used in situ hybridization to measure expression of these molecular markers. c-myc mRNA was detected in 18 of 59 (31%) cases, and was significantly associated with shorter patient survival times on both univariate and multivariate analyses (p = 0.04). The presence of c-myc mRNA was also significantly associated with tumor anaplasia. While survival rates were higher for patients with low N-myc or high TrkC expression, these differences were not statistically significant. The group of patients with either moderate or severely anaplastic tumors showed only a trend towards shorter survival (p = 0.11). However, severe anaplasia alone was significantly prognostic (p = 0.002). Given the prognostic import of c-myc, we investigated 2 potential mechanisms by which its expression might be regulated: Wnt signaling and Mxi-1 mutation. Nuclear translocation of beta-catenin, a marker of Wnt pathway activation, was more common in medulloblastomas with high c-myc than in tumors overall, but the difference was not statistically significant. No Mxi-1 mutations were detected in the 22 cases examined. The association we describe between c-myc expression, tumor anaplasia, and worse clinical outcomes provides further evidence for the importance of this oncogene in medulloblastoma pathobiology.

The BAX/BAK-like protein BOK is a prognostic marker in colorectal cancer.

PubMed

Carberry, Steven; D'Orsi, Beatrice; Monsefi, Naser; Salvucci, Manuela; Bacon, Orna; Fay, Joanna; Rehm, Markus; McNamara, Deborah; Kay, Elaine W; Prehn, Jochen H M

2018-01-26

The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members of the BCL-2 protein family. Activation of this death pathway plays a crucial role in cancer progression and chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that stage II and III colorectal cancer patients possessed decreased levels of BOK protein in their tumours compared to matched normal tissue. BOK protein levels in tumours were also prognostic of clinical outcome but increased BOK protein levels surprisingly associated with earlier disease recurrence and reduced overall survival. We found no significant association of BOK protein tumour levels with ER stress markers GRP78 or GRP94 or with cleaved caspase-3. In contrast, BOK protein levels correlated with Calreticulin. These data indicate BOK as a prognostic marker in colorectal cancer and suggest that different activities of BOK may contribute to cancer progression and prognosis.

DAPK1 as an independent prognostic marker in liver cancer.

PubMed

Li, Ling; Guo, Libin; Wang, Qingshui; Liu, Xiaolong; Zeng, Yongyi; Wen, Qing; Zhang, Shudong; Kwok, Hang Fai; Lin, Yao; Liu, Jingfeng

2017-01-01

The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort ( n  = 115;  p  = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression ( p  = 0.002) and overall survival ( p  = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PubMed Central

Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

PubMed

Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

2015-11-10

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value

Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank

2011-02-01

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biologicalmore » markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.« less

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

PubMed

Liang, Ya-Nan; Liu, Yu; Wang, Letian; Yao, Guodong; Li, Xiaobo; Meng, Xiangning; Wang, Fan; Li, Ming; Tong, Dandan; Geng, Jingshu

2018-06-01

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Poorly Differentiated Clusters Predict Colon Cancer Recurrence: An In-Depth Comparative Analysis of Invasive-Front Prognostic Markers.

PubMed

Konishi, Tsuyoshi; Shimada, Yoshifumi; Lee, Lik Hang; Cavalcanti, Marcela S; Hsu, Meier; Smith, Jesse Joshua; Nash, Garrett M; Temple, Larissa K; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Vakiani, Efsevia; Gonen, Mithat; Shia, Jinru; Weiser, Martin R

2018-06-01

This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed. Prognostic accuracies for recurrence-free survival (RFS) were compared, and interobserver agreement among 3 pathologists was assessed. The study cohort consisted of 851 patients. Although all the histologic markers except WHO grade were significantly associated with RFS (PDCs, tumor budding, perineural invasion, and desmoplastic reaction: P<0.001; Crohn-like lymphoid reaction: P=0.021), PDCs (grade 1 [G1]: n=581; G2: n=145; G3: n=125) showed the largest separation of 3-year RFS in the full cohort (G1: 94.1%; G3: 63.7%; hazard ratio [HR], 6.39; 95% confidence interval [CI], 4.11-9.95; P<0.001), stage II patients (G1: 94.0%; G3: 67.3%; HR, 4.15; 95% CI, 1.96-8.82; P<0.001), and stage III patients (G1: 89.0%; G3: 59.4%; HR, 4.50; 95% CI, 2.41-8.41; P<0.001). PDCs had the highest prognostic accuracy for RFS with the concordance probability estimate of 0.642, whereas WHO grade had the lowest. Interobserver agreement was the highest for PDCs, with a weighted kappa of 0.824. The risk of recurrence over time peaked earlier for worse PDCs grade. Our findings indicate that PDCs are the best invasive-front histologic marker in terms of prognostic accuracy and interobserver agreement. PDCs may replace WHO grade as a prognostic indicator.

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

PubMed

Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

2014-01-01

Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS. We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma.

PubMed

Mendrzyk, Frank; Radlwimmer, Bernhard; Joos, Stefan; Kokocinski, Felix; Benner, Axel; Stange, Daniel E; Neben, Kai; Fiegler, Heike; Carter, Nigel P; Reifenberger, Guido; Korshunov, Andrey; Lichter, Peter

2005-12-01

Medulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms. We performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival. Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02). We identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.

[MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia].

PubMed

Winkler, Melissa M; Weis, Meike; Henzler, Claudia; Weiß, Christel; Kehl, Sven; Schoenberg, Stefan O; Neff, Wolfgang; Schaible, Thomas

2017-03-01

Background Our aim was to evaluate the prognostic value of magnetic resonance imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) as a marker for development of chronic lung disease (CLD) in fetuses with congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were measured and the individual FLV/FBV ratio was calculated in 132 fetuses. Diagnosis of CLD was established following prespecified criteria and graded into mild/moderate/severe if present. Logistic regression analysis was used to calculate the probability of postnatal development of CLD in dependence of the FLV/FBV ratio. Receiver operating characteristic curves were analysed by calculating the area under the curve to evaluate the prognostic accuracy of this marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD was significantly associated with thoracic herniation of liver parenchyma (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001) and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV to FBV is a highly valuable prenatal parameter for development of CLD. The ratio is helpful for early therapeutic decisions by estimating the probability to develop CLD. Perinatally, gestational age at delivery and ECMO requirement are useful additional parameters to further improve prediction of CLD. © Georg Thieme Verlag KG Stuttgart · New York.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

PubMed

Kato, Shingo; Akimoto, Kazunori; Nagashima, Yoji; Ishiguro, Hitoshi; Kubota, Kensuke; Kobayashi, Noritoshi; Hosono, Kunihiro; Watanabe, Seitaro; Sekino, Yusuke; Sato, Takamitsu; Sasaki, Kazunori; Nakaigawa, Noboru; Kubota, Yoshinobu; Inayama, Yoshiaki; Endo, Itaru; Ohno, Shigeo; Maeda, Shin; Nakajima, Atsushi

2013-01-01

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients.

PubMed

Culpin, Rachel E; Sieniawski, Michal; Angus, Brian; Menon, Geetha K; Proctor, Stephen J; Milne, Paul; McCabe, Kate; Mainou-Fowler, Tryfonia

2013-12-01

To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized. © 2013 John Wiley & Sons Ltd.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

PubMed

Bossard, N; Descotes, F; Bremond, A G; Bobin, Y; De Saint Hilaire, P; Golfier, F; Awada, A; Mathevet, P M; Berrerd, L; Barbier, Y; Estève, J

2003-11-01

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

The prognostic value of biological markers in paediatric Hodgkin lymphoma.

PubMed

Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Buffardi, Salvatore; Garaventa, Alberto; Bottigliero, Gaetano; Bianchi, Maurizio; Zecca, Marco; Locatelli, Franco; Pession, Andrea; Pillon, Marta; Favre, Claudio; D'Amico, Salvatore; Provenzi, Massimo; Trizzino, Angela; Zanazzo, Giulio Andrea; Sau, Antonella; Santoro, Nicola; Murgia, Giulio; Casini, Tommaso; Mascarin, Maurizio; Burnelli, Roberta

2016-01-01

Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glasgow Prognostic Score as a Prognostic Clinical Marker in T4 Esophageal Squamous Cell Carcinoma.

PubMed

Ohira, Masaichi; Kubo, Naoshi; Masuda, Go; Yamashita, Yoshito; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

2015-09-01

Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented. This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP >10 mg/l or albumin <35 g/l, or CRP >10 mg/l and albumin <35 g/l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses. Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p < 0.01). On multivariate analysis, good response to CRT [hazard ratio (HR) =0.449, p<0.01], GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, p<0.01) were significant prognostic factors, whereas PNI was not. The GPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy. Copyright© 2015 International Institute of

Prognostic Value of Molecular Markers and Implication for Molecular Targeted Therapies in Nasopharyngeal Carcinoma: An Update in an Era of New Targeted Molecules Development.

PubMed

Liu, Mu-Tai; Chen, Mu-Kuan; Huang, Chia-Chun; Huang, Chao-Yuan

2015-02-01

The aim of the study was to evaluate the prognostic significance of molecular biomarkers which could provide information for more accurate prognostication and development of novel therapeutic strategies for nasopharyngeal carcinoma (NPC). NPC is a unique malignant epithelial carcinoma of head and neck region, with an intimate association with the Epstein-Barr virus (EBV). Currently, the prediction of NPC prognosis is mainly based on the clinical TNM staging; however, NPC patients with the same clinical stage often present different clinical outcomes, suggesting that the TNM stage is insufficient to precisely predict the prognosis of this disease. In this review, we give an overview of the prognostic value of molecular markers in NPC and discuss potential strategies of targeted therapies for treatment of NPC. Molecular biomarkers, which play roles in abnormal proliferation signaling pathways (such as Wnt/β-catenin pathway), intracellular mitogenic signal aberration (such as hypoxia-inducible factor (HIF)-1α), receptor-mediated aberrations (such as vascular endothelial growth factor (VEGF)), tumor suppressors (such as p16 and p27 activity), cell cycle aberrations (such as cyclin D1 and cyclin E), cell adhesion aberrations (such as E-cadherin), apoptosis dysregualtion (such as survivin) and centromere aberration (centromere protein H), are prognostic markers for NPC. Plasma EBV DNA concentrations and EBV-encoded latent membrane proteins are also prognostic markers for NPC. Implication of molecular targeted therapies in NPC was discussed. Such therapies could have potential in combination with different cytotoxic agents to combat and eradicate tumor cells. In order to further improve overall survival for patients with loco-regionally advanced NPC, the development of innovative strategies, including prognostic molecular markers and molecular targeted agents is needed.

Identification and validation of novel prognostic markers in Renal Cell Carcinoma.

PubMed

Rabjerg, Maj

2017-10-01

Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system. Other comprehensive staging modalities have emerged and have been implemented in an attempt to improve prognostication by combining other pathological and clinical variables, including Fuhrman nuclear grade and Leibovich score. However, even early stage tumors remain at risk of metastatic progression after surgical resection and 20-40% of patients undergoing nephrectomy for clinically localized RCC will develop a recurrence. Identifying this high-risk group of RCC patients remains a challenge. Hence, novel molecular prognostic biomarkers are needed to better predict clinical outcomes. An intensive search within this field has been ongoing in the past few years, and the three main predictive and prognostic markers validated in RCC are Von Hippel Lindau (VHL), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CAIX). Nonetheless, the use of these is still debated and none of them have yet been implemented in clinical routine. RCC is resistant to conventional oncological therapies, such as chemotherapy and radiation. The availability of novel targeted therapies directed against tumorigenic and angiogenic pathways have increased over the last years, and the outcome of patients with advanced RCC has significantly improved as a consequence. Unfortunately, all patients eventually become resistant. Thus, the development of novel targeted therapies is of great importance. The aim of this thesis was therefore to contribute in the search for novel

SMAD4 is a potential prognostic marker in human breast carcinomas

PubMed Central

Liu, Nan-nan; Xi, Yue; Callaghan, Michael U.; Fribley, Andrew; Moore-Smith, Lakisha; Zimmerman, Jacquelyn W.; Pasche, Boris

2014-01-01

SMAD4 is a downstream mediator of transforming growth factor beta. While its tumor suppressor function has been investigated as a prognostic biomarker in several human malignancies, its role as a prognostic marker in breast carcinoma is still undefined. We investigated SMAD4 expression in breast carcinoma samples of different histologic grades to evaluate the association between SMAD4 and outcome in breast cancer. We also investigated the role of SMAD4 expression status in MDA-MB-468 breast cancer cells in responding to TGF-β stimulation. SMAD4 expression was assessed in 53 breast ductal carcinoma samples and in the surrounding normal tissue from 50 of the samples using immunohistochemistry, Western blot, and real-time PCR. TGF-β-SMAD and non-SMAD signaling was assessed by Western blot in MDA-MB-468 cells with and without SMAD4 restoration. SMAD4 expression was reduced in ductal breast carcinoma as compared to surrounding uninvolved ductal breast epithelia (p <0.05). SMAD4 expression levels decreased from Grade 1 to Grade 3 ductal breast carcinoma as assessed by immunohistochemistry (p <0.05). Results were recapitulated by tissue array. In addition, immunohistochemistry results were further confirmed at the protein and mRNA level. We then found that non-SMAD MEK/MAPK signaling was significantly different between SMAD4 expressing MDA-MB-468 cells and SMAD4-null MDA-MB-468 cells. This is the first study indicating that SMAD4 plays a key role in shifting MAPK signaling. Further, we have demonstrated that SMAD4 has a potential role in the development of breast carcinoma and SMAD4 was a potential prognostic marker of breast carcinoma. Our findings further support the role of SMAD4 in breast carcinoma development. In addition, we observed an inverse relationship between SMAD4 levels and breast carcinoma histological grade. Our finding indicated that SMAD4 expression level in breast cancer cells played a role in responding non-SMAD signaling but not the canonic SMAD

Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

PubMed

Monteiro de Oliveira Novaes, Jose Augusto; William, William N

2016-10-01

Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer.

PubMed

Grönberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fjällskog, Marie-Louise

2017-01-01

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

Mental health symptoms as prognostic risk markers of all-cause and psychiatric sickness absence in office workers.

PubMed

Roelen, Corné A M; Hoedeman, Rob; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Bültmann, Ute

2014-02-01

To investigate mental health symptoms as prognostic risk markers of all-cause and psychiatric sickness absence (SA). Mental health symptoms were measured in 1137 office workers with the Four-Dimensional Symptom Questionnaire (4DSQ), including scales for distress, depression, anxiety and somatization. The total number of SA days was accumulated prospectively on the individual level and high SA was defined as ≥30 SA days during 1-year follow-up. Psychiatric SA was also tallied on the individual level during 1-year follow-up. Baseline 4DSQ scores were associated with high all-cause SA and psychiatric SA by logistic regression analysis. The Hosmer-Lemeshow test and calibration slope were used to assess the accuracy of predictions by 4DSQ scores. The ability of 4DSQ scores to discriminate high-risk from low-risk employees was estimated by the area under the receiver operating characteristic curve. Six hundred thirty-three office workers (56%) participated in the study. All 4DSQ scales were prospectively associated with high all-cause SA and with psychiatric SA. Distress and somatization scores showed acceptable calibration, but failed to discriminate between office workers with and without high all-cause SA. The distress scale did show adequate calibration (calibration slope = 0.95) and discrimination (area under the receiver operating characteristic curve = 0.71) for psychiatric SA. Distress was a valid prognostic risk marker for identifying office workers at work, but at risk of future psychiatric SA. Further research is necessary to investigate the prognostic performance of distress as risk marker of psychiatric SA in other working populations and to determine cut-off points for distress.

Entropy-Based Adaptive Nuclear Texture Features are Independent Prognostic Markers in a Total Population of Uterine Sarcomas

PubMed Central

Nielsen, Birgitte; Hveem, Tarjei Sveinsgjerd; Kildal, Wanja; Abeler, Vera M; Kristensen, Gunnar B; Albregtsen, Fritz; Danielsen, Håvard E; Rohde, Gustavo K

2015-01-01

Nuclear texture analysis measures the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image and is a promising quantitative tool for prognosis of cancer. The aim of this study was to evaluate the prognostic value of entropy-based adaptive nuclear texture features in a total population of 354 uterine sarcomas. Isolated nuclei (monolayers) were prepared from 50 µm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices, and two superior adaptive texture features were calculated from each matrix. The 5-year crude survival was significantly higher (P < 0.001) for patients with high texture feature values (72%) than for patients with low feature values (36%). When combining DNA ploidy classification (diploid/nondiploid) and texture (high/low feature value), the patients could be stratified into three risk groups with 5-year crude survival of 77, 57, and 34% (Hazard Ratios (HR) of 1, 2.3, and 4.1, P < 0.001). Entropy-based adaptive nuclear texture was an independent prognostic marker for crude survival in multivariate analysis including relevant clinicopathological features (HR = 2.1, P = 0.001), and should therefore be considered as a potential prognostic marker in uterine sarcomas. © The Authors. Published 2014 International Society for Advancement of Cytometry PMID:25483227

Cancer molecular markers: A guide to cancer detection and management.

PubMed

Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

2018-02-08

Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Recent advances in oncology have led to the discovery of cancer markers that has allowed early detection and targeted therapy of tumors. In this context, current review provides a detail outlook on various molecular markers for diagnosis, prognosis and management of therapeutic response in cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

PubMed

Frankenstein, Lutz; Meyer, Franz Joachim; Sigg, Caroline; Nelles, Manfred; Schellberg, Dieter; Remppis, Andrew; Katus, Hugo A; Zugck, Christian

2008-04-01

Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.

Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer.

PubMed

Chen, Jie; Li, Yan; Zheng, Qiupeng; Bao, Chunyang; He, Jian; Chen, Bin; Lyu, Dongbin; Zheng, Biqiang; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; He, Xianghuo; Shi, Yingqiang; Huang, Shenglin

2017-03-01

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

PubMed Central

Kwak, Yoonjin; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

2016-01-01

Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC. PMID:27835889

Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

PubMed

Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-11-25

The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.

Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

NASA Astrophysics Data System (ADS)

Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

2016-04-01

Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study.

PubMed

Wager, M; Menei, P; Guilhot, J; Levillain, P; Michalak, S; Bataille, B; Blanc, J-L; Lapierre, F; Rigoard, P; Milin, S; Duthe, F; Bonneau, D; Larsen, C-J; Karayan-Tapon, L

2008-06-03

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

PubMed

Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

2016-11-01

Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

PubMed

Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-05-10

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P< 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21

Prognostic significance of aberrant gene methylation in gastric cancer.

PubMed

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer.

Prognostic significance of aberrant gene methylation in gastric cancer

PubMed Central

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer. PMID:22206050

Glucose transporter-1 as an independent prognostic marker for cancer: a meta-analysis

PubMed Central

Zhao, Zheng-Xiao; Lu, Lin-Wei; Qiu, Jian; Li, Qiu-Ping; Xu, Fei; Liu, Bao-Jun; Dong, Jing-Cheng; Gong, Wei-Yi

2018-01-01

Objective Glucose transporter-1 (GLUT-1) as the major glucose transporter present in human cells is found overexpressed in a proportion of human malignancies. This meta-analysis is attempted to assess the prognostic significance of GLUT-1 for survival in various cancers. Materials and Methods We conducted an electronic search using the databases PubMed, Embase and Web of Science, from inception to Oct 20th, 2016. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results Fourty-one studies with a total of 4794 patients were included. High GLUT-1 expression was significantly associated with poorer prognosis [overall survival: HR = 1.833 (95% CI: 1.597–2.069, P < 0.0001); disease-free survival: HR = 1.838 (95% CI: 1.264–2.673, P < 0.0001); progression-free survival: HR = 2.451 (95% CI: 1.668–3.233, P < 0.0001); disease specific survival: HR = 1.96 (95% CI: 1.05–2.871, P < 0.0001)]. Conclusions High GLUT-1 expression may be an independent prognostic marker to predict poor survival in various types of cancers. Further clinical trials with high quality need to be conducted to confirm our conclusion. PMID:29416806

The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

PubMed

Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

2015-10-01

Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Realizing the Translational Potential of Telomere Length Variation as a Tissue Based Prognostic Marker for Prostate Cancer

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-12-1-0545 TITLE: Realizing the Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for...30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Realizing the Translational Potential of Telomere Length Variation as a Tissue...HPFS), whether the combination of telomere length variability in prostate cancer cells and short telomere length in cancer-associated stromal cells is

Canine Distemper Virus Antigen Detection in External Epithelia of Recently Vaccinated, Sick Dogs by Fluorescence Microscopy Is a Valuable Prognostic Indicator

PubMed Central

Neel, Tina

2014-01-01

Currently, there are no reliable predictors of the clinical outcomes of domesticated dogs that have been recently vaccinated against canine distemper virus (CDV) and develop respiratory disease. In this study, vaccinated dogs from Oklahoma City that were showing clinical signs of respiratory disease were evaluated for CDV antigen using a direct fluorescent antibody test (FAT). Clinical outcomes after standard symptomatic therapy for respiratory disease were recorded, and a statistical analysis of the results was performed. We present our study showing that CDV FAT results were predictive of clinical recovery (prognostic indicator, prospects of clinical recovery) among vaccinated dogs showing clinical signs of respiratory disease. Negative CDV FAT results equated to 80% chances of recovery after symptomatic therapy, compared to 55% chances of recovery when the CDV FAT results were positive. Based on the results of this study, we show that veterinarians can make better informed decisions about the clinical outcomes of suspected CDV cases, with 2-h turnaround times, by using the CDV FAT. Thus, antemortem examination with the CDV FAT on external epithelia of recently vaccinated, sick dogs is a clinically useful diagnostic test and valuable prognostic indicator for veterinarians. Application of the CDV FAT to these samples avoids unnecessary euthanasia of dogs with suspected CDV. PMID:25428156

Additional Prognostic Value of SUVmax Measured by F-18 FDG PET/CT over Biological Marker Expressions in Surgically Resected Cervical Cancer Patients.

PubMed

Yun, Man Soo; Kim, Seong-Jang; Pak, Kyoungjune; Lee, Chang Hun

2015-01-01

We compared the prognostic ability of the maximum standardized uptake value (SUVmax) and various biological marker expressions to predict recurrence in patients with surgically resected cervical cancer. A retrospective review identified 60 patients with cervical cancer who received [18F]fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) at the time of the diagnosis of cancer. The SUVmax, expressions of carbonic anhydrase-IX (CA-IX), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF), and known prognostic factors were investigated. The median follow-up time was 22.2 months (range 3.4-43.1 months). Using univariate analyses, the stage (stage II, p = 0.0066), SUVmax (> 6, p = 0.027), parametrial involvement (p < 0.0001), and positivity for CA-IX (p = 0.0191) were associated with recurrences of cervical cancer. With the Cox proportional hazard regression model, the SUVmax was a potent predictor for disease-free survival (DFS). Although CA-IX expression was related to DFS in the current study, the potent predictor for DFS was SUVmax. Therefore, SUVmax is of greater prognostic value than biological marker expression in patients with surgically resected cervical cancer. © 2015 S. Karger GmbH, Freiburg.

Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia.

PubMed

Gelaleti, Gabriela B; Granzotto, Adriana; Leonel, Camila; Jardim, Bruna V; Moschetta, Marina G; Carareto, Claudia M A; Zuccari, Debora Ap P C

2014-01-01

The genome of mammals is characterized by a large number of non-LTR retrotransposons, and among them, the CAN SINEs are characteristics of the canine species. Small amounts of DNA freely circulate in normal blood serum and high amounts are found in human patients with cancer, characterizing it as a candidate tumor-biomarker. The aim of this study was to estimate, through its absolute expression, the number of copies of CAN SINE sequences present in free circulating DNA of female dogs with mammary cancer, in order to correlate with the clinical and pathological characteristics and the follow-up period. The copy number of CAN SINE sequences was estimated by qPCR in 28 female dogs with mammary neoplasia. The univariate analysis showed an increased number of copies in female dogs with mammary tumor in female dogs >10 years old (p=0.02) and tumor time >18 months (p<0.05). The Kaplan-Meier test demonstrated a negative correlation between an increased number of copies and survival time (p=0.03). High amounts of CAN SINE fragments can be good markers for the detection of tumor DNA in blood and may characterize it as a marker of poor prognosis, being related to female dogs with shorter survival times. This estimate can be used as a prognostic marker in non-invasive breast cancer research and is useful in predicting tumor progression and patient monitoring.

Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients.

PubMed

Hendriks, Rianne J; Dijkstra, Siebren; Smit, Frank P; Vandersmissen, Johan; Van de Voorde, Hendrik; Mulders, Peter F A; van Oort, Inge M; Van Criekinge, Wim; Schalken, Jack A

2018-04-01

Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. In this prospective study, patients were included before starting new treatment after developing CRPC. The blood samples were collected prior to start of the treatment and at three time points thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a methylation-specific PCR, bisulfate modification was carried out. The median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC patients (n = 47) were higher than in controls (n = 30). In the survival analysis, the group with baseline marker levels below median had significant less PCa-related deaths (P-values <0.02) and did not reach the median survival point. The survival distributions for the groups were statistically significant for the cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 + APC (P-values <0.03). Furthermore, there were strong positive correlations between PSA and marker response after starting treatment (P-values <0.04). In conclusion, this study showed the kinetics of methylated cfDNA (GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore, the value of the markers before treatment is prognostic for overall survival. These results are promising for developing a test to guide treatment-decision-making for CRPC patients. © 2018 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

DTIC Science & Technology

2015-10-01

Award Number: W81XWH-12-1-0545 TITLE: Realizing the Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for...COVERED 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0545 Realizing the Translational Potential of Telomere Length...14. ABSTRACT We are testing, in prospective studies from Hopkins (Brady) and Harvard (PHS, HPFS), whether the combination of telomere length

Imaging markers for Alzheimer disease

PubMed Central

Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles

2013-01-01

Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

PubMed

Reddy, Sreekanth P; Britto, Ramona; Vinnakota, Katyayni; Aparna, Hebbar; Sreepathi, Hari Kishore; Thota, Balaram; Kumari, Arpana; Shilpa, B M; Vrinda, M; Umesh, Srikantha; Samuel, Cini; Shetty, Mitesh; Tandon, Ashwani; Pandey, Paritosh; Hegde, Sridevi; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Kondaiah, Paturu; Somasundaram, Kumaravel; Rao, M R Satyanarayana

2008-05-15

Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM

Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with Type 2 Diabetes

PubMed Central

2012-01-01

Background Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients. Methods We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10 years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61 ± 16 months. Results A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0 ± 4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59 ± 0.07 (P = 0.21). Among different vascular assessments, CACS > 40 had the best prognostic value (AUC 0.81 ± 0.06, P < 0.01) and offered significantly better accuracy in prediction compared with FRS (P = 0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS > 40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P = 0.002). Conclusions In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS > 40 was an independent predictor for atherosclerotic events. PMID:22900680

Canine distemper virus antigen detection in external epithelia of recently vaccinated, sick dogs by fluorescence microscopy is a valuable prognostic indicator.

PubMed

Kapil, Sanjay; Neel, Tina

2015-02-01

Currently, there are no reliable predictors of the clinical outcomes of domesticated dogs that have been recently vaccinated against canine distemper virus (CDV) and develop respiratory disease. In this study, vaccinated dogs from Oklahoma City that were showing clinical signs of respiratory disease were evaluated for CDV antigen using a direct fluorescent antibody test (FAT). Clinical outcomes after standard symptomatic therapy for respiratory disease were recorded, and a statistical analysis of the results was performed. We present our study showing that CDV FAT results were predictive of clinical recovery (prognostic indicator, prospects of clinical recovery) among vaccinated dogs showing clinical signs of respiratory disease. Negative CDV FAT results equated to 80% chances of recovery after symptomatic therapy, compared to 55% chances of recovery when the CDV FAT results were positive. Based on the results of this study, we show that veterinarians can make better informed decisions about the clinical outcomes of suspected CDV cases, with 2-h turnaround times, by using the CDV FAT. Thus, antemortem examination with the CDV FAT on external epithelia of recently vaccinated, sick dogs is a clinically useful diagnostic test and valuable prognostic indicator for veterinarians. Application of the CDV FAT to these samples avoids unnecessary euthanasia of dogs with suspected CDV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

PubMed

Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-22

Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer.

PubMed

Blum, Craig; Graham, Amanda; Yousefzadeh, Matt; Shrout, Jessica; Benjamin, Katie; Krishna, Murli; Hoda, Raza; Hoda, Rana; Cole, David J; Garrett-Mayer, Elizabeth; Reed, Carolyn; Wallace, Michael; Mitas, Michael

2008-09-01

Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making.

The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer

PubMed Central

BLUM, CRAIG; GRAHAM, AMANDA; YOUSEFZADEH, MATT; SHROUT, JESSICA; BENJAMIN, KATIE; KRISHNA, MURLI; HODA, RAZA; HODA, RANA; COLE, DAVID J.; GARRETT-MAYER, ELIZABETH; REED, CAROLYN; WALLACE, MICHAEL; MITAS, MICHAEL

2012-01-01

Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making. PMID:18695889

The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin

2009-06-01

Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16{sup INK4a} staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO{sub 2} and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumorsmore » had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16{sup INK4a} staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16{sup INK4a} staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO{sub 2} or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.« less

Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.

PubMed

Solé, Francesc; Luño, Elisa; Sanzo, Carmen; Espinet, Blanca; Sanz, Guillermo F; Cervera, José; Calasanz, María José; Cigudosa, Juan Cruz; Millà, Fuensanta; Ribera, Josep Maria; Bureo, Encarna; Marquez, Maria Luisa; Arranz, Eva; Florensa, Lourdes

2005-09-01

The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.

Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

PubMed

Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

2018-01-01

Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

PubMed Central

Maruyama, Tessho; Nishihara, Kazuhide; Umikawa, Masato; Arasaki, Akira; Nakasone, Toshiyuki; Nimura, Fumikazu; Matayoshi, Akira; Takei, Kimiko; Nakachi, Saori; Kariya, Ken-Ichi; Yoshimi, Naoki

2018-01-01

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2−ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=−0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease

PubMed Central

Tarawneh, Rawan; D’Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M.; Zipfel, Gregory J.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.

2016-01-01

IMPORTANCE Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. OBJECTIVE To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. MAIN OUTCOMES AND MEASURES Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls overtime. RESULTS A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64–0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = −0.38, P = .02; hippocampal volumes: adjusted r = −0.36, P = .03; entorhinal volumes: adjusted r = −0.46, P = .006; and parahippocampal volumes: adjusted r = −0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease.

PubMed

Tarawneh, Rawan; D'Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M; Zipfel, Gregory J; Ladenson, Jack H; Morris, John C; Holtzman, David M

2016-05-01

Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls over time. A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64-0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = -0.38, P = .02; hippocampal volumes: adjusted r = -0.36, P = .03; entorhinal volumes: adjusted r = -0.46, P = .006; and parahippocampal volumes: adjusted r = -0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

PubMed

Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-11-25

Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme

PubMed Central

Rosati, Anna; Poliani, Pietro Luigi; Todeschini, Alice; Cominelli, Manuela; Medicina, Daniela; Cenzato, Marco; Simoncini, Edda Lucia; Magrini, Stefano Maria; Buglione, Michela; Grisanti, Salvatore; Padovani, Alessandro

2013-01-01

Abstract Background Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival. Methods We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression. Results Median age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5–58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O6-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses. Conclusions Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM. PMID:23410662

A comparison of prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill: a cohort study.

PubMed

Ho, Kwok M; Lan, Norris S H; Williams, Teresa A; Harahsheh, Yusra; Chapman, Andrew R; Dobb, Geoffrey J; Magder, Sheldon

2016-01-01

This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach

Evaluation of the prognostic value of platelet to lymphocyte ratio in patients with hepatocellular carcinoma.

PubMed

Wang, Yuchen; Attar, Bashar M; Fuentes, Harry E; Jaiswal, Palashkumar; Tafur, Alfonso J

2017-12-01

Hepatocellular carcinoma (HCC) is increasingly common, potentially fatal cancer type globally. Platelet-lymphocyte ratio (PLR) as a biomarker for systemic inflammation has recently been recognized as a valuable prognostic marker in multiple cancer types. The aim of the present study was to assess the prognostic value of PLR in HCC patients and determine the optimal cut-off value for risk stratification. We retrospectively analyzed patients with diagnosis of HCC (screened by ICD-9 code, confirmed with radiographic examination and/or biopsy) at a large public hospital during 15 years (Jan 2000 through July 2015). PLR, among other serology laboratory values were collected at diagnosis of HCC. Its association with overall survival was evaluated with Cox proportional hazard model. Among 270 patients with HCC, 57 (21.1%) patients died within an average follow-up of 11.9 months. PLR at diagnosis was significantly different between survivors and deceased (128.9 vs. 186.7; P=0.003). In multivariate analysis, aspartate transaminase (AST) (HR 2.022, P<0.001) and PLR (HR 1.768, P=0.004) independently predicted mortality. The optimal cut-off value for PLR was determined to be 220 by receiver-operating characteristics curve, and high PLR group had significantly higher mortality (HR 3.42, P<0.001). Our results indicated that elevated PLR at diagnosis above 220 predicted poor prognosis in HCC patients. PLR is a low-cost and convenient tool, which may serve as a useful prognostic marker for HCC.

Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).

PubMed

Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo

2016-02-01

Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. Copyright © 2015. Published by Elsevier Inc.

CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

PubMed Central

Palmi, Chiara; Savino, Angela M.; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U.; Bugarin, Cristina; Mina, Pamela Della; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Nigro, Luca Lo; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C.; Santoro, Nicola; Testi, Anna M.; Ziino, Ottavio; Kulozik, Andreas E.; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G.; Stanulla, Martin; Conter, Valentino; te Kronnie, Geertruy; Cazzaniga, Giovanni

2016-01-01

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway. PMID:27449287

CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia.

PubMed

Palmi, Chiara; Savino, Angela M; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U; Bugarin, Cristina; Della Mina, Pamela; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Lo Nigro, Luca; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C; Santoro, Nicola; Testi, Anna M; Ziino, Ottavio; Kulozik, Andreas E; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G; Stanulla, Martin; Conter, Valentino; Te Kronnie, Geertruy; Cazzaniga, Giovanni

2016-09-13

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL.We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers.Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated.Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib.In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway.

Macrophage Migration Inhibitory Factor and Stearoyl-CoA Desaturase 1: Potential Prognostic Markers for Soft Tissue Sarcomas Based on Bioinformatics Analyses

PubMed Central

Takahashi, Hiro; Nakayama, Robert; Hayashi, Shuhei; Nemoto, Takeshi; Murase, Yasuyuki; Nomura, Koji; Takahashi, Teruyoshi; Kubo, Kenji; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sueo, Takuya; Takahashi, Anna; Tsutsumiuchi, Kaname; Ohta, Tsutomu; Kawai, Akira; Sugita, Shintaro; Yamamoto, Shinjiro; Kobayashi, Takeshi; Honda, Hiroyuki; Yoshida, Teruhiko; Hasegawa, Tadashi

2013-01-01

The diagnosis and treatment of soft tissue sarcomas (STSs) has been particularly difficult, because STSs are a group of highly heterogeneous tumors in terms of histopathology, histological grade, and primary site. Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis, treatment selection, and investigation of therapeutic targets. We had previously developed a novel bioinformatics method for marker gene selection and applied this method to gene expression data from STS patients. This previous analysis revealed that the extracted gene combination of macrophage migration inhibitory factor (MIF) and stearoyl-CoA desaturase 1 (SCD1) is an effective diagnostic marker to discriminate between subtypes of STSs with highly different outcomes. In the present study, we hypothesize that the combination of MIF and SCD1 is also a prognostic marker for the overall outcome of STSs. To prove this hypothesis, we first analyzed microarray data from 88 STS patients and their outcomes. Our results show that the survival rates for MIF- and SCD1-positive groups were lower than those for negative groups, and the p values of the log-rank test are 0.0146 and 0.00606, respectively. In addition, survival rates are more significantly different (p = 0.000116) between groups that are double-positive and double-negative for MIF and SCD1. Furthermore, in vitro cell growth inhibition experiments by MIF and SCD1 inhibitors support the hypothesis. These results suggest that the gene set is useful as a prognostic marker associated with tumor progression. PMID:24167613

Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

PubMed

Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

2018-05-02

The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Hilmersson, Katarzyna Said; Andersson, Roland

2018-01-01

To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous cell carcinoma.

PubMed

Chung, Y; Law, S; Kwong, D L W; Luk, J M

2011-01-01

E-cadherin is a well-documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa degradation fragment, known as soluble E-cadherin (s-Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s-Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s-Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s-Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s-Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026-1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine.

PubMed

Dantan, Etienne; Foucher, Yohann; Lorent, Marine; Giral, Magali; Tessier, Philippe

2018-06-01

Defining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice.

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

PubMed Central

Heaphy, Christopher M.; Yoon, Ghil Suk; Peskoe, Sarah B.; Joshu, Corinne E.; Lee, Thomas K.; Giovannucci, Edward; Mucci, Lorelei A.; Kenfield, Stacey A.; Stampfer, Meir J.; Hicks, Jessica L.; De Marzo, Angelo M.; Platz, Elizabeth A.; Meeker, Alan K.

2013-01-01

Current prognostic indicators are imperfect predictors of outcome in men with clinicallylocalized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. PMID:23779129

Downregulation of microRNA-206 is a potent prognostic marker for patients with gastric cancer.

PubMed

Yang, Qi; Zhang, Chao; Huang, Bo; Li, Huiyan; Zhang, Rong; Huang, Yuxin; Wang, Jingjie

2013-08-01

MicroRNA-206 (miR-206), as a homolog of miR-1, plays important roles in tumorigenesis and tumor progression of various human malignancies, including breast cancer, endometrial endometrioid carcinoma, rhabdomyosarcoma, glioma, lung cancer, and laryngeal cancer. However, its involvement in gastric cancer has remained unclear. To examine the expression patterns and clinical implications of miR-206 in gastric cancer. Quantitative RT-PCR was performed to evaluate the expression levels of miR-206 in 98 pairs of gastric cancer and normal adjacent mucosa. In addition, the clinicopathologic significance and the prognostic value of miR-206 expression were further determined. At first, miR-206 expression was significantly downregulated in gastric cancer tissues when compared with normal adjacent mucosa (P<0.001). Next, tumors with low miR-206 expression had a greater extent of lymph node metastasis (P=0.01), presence of venous invasion (P=0.008), and hematogenous recurrence (P=0.01), and were at a worse stage (P=0.03) than the tumors with a high miR-206 expression. Then, the gastric cancer patients with a low miR-206 expression had shorter overall survival than those with a high miR-206 expression (P=0.02). Furthermore, multivariate analysis showed that miR-206 expression was an independent prognostic factor for patients with gastric cancer. Our results strongly suggest that the downregulation of miR-206 was significantly correlated with tumor progression and may be a potent prognostic marker of gastric cancer. miR-206 might serve as a promising therapeutic target for the treatment of this cancer.

Influence of prognostic nutritional index and tumor markers on survival in gastric cancer surgery patients.

PubMed

Saito, Hiroaki; Kono, Yusuke; Murakami, Yuki; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Osaki, Tomohiro

2017-05-01

Blood analytes are easily used in routine clinical practice. Tumor markers (TMs) are useful in diagnosing, treating, and predicting prognosis of gastric cancer (GC). The prognostic nutritional index (PNI) was also recently found to be useful in predicting GC prognosis. The PNI and serum levels of CEA and CA19-9 of 453 patients with GC were measured to examine correlations between those levels and patients' prognoses. Of the 453 patients, 84 (18.5%) were positive for CEA and/or CA19-9 and therefore considered positive for TMs. Prognosis of patients who were TM+ was significantly worse than for those who were TM-. Mean PNI was 48.2 (range 27.7-63.6). ROC analysis indicated that 46.7 was the optimal PNI cutoff value. Prognosis of patients in the PNI Low group (<46.7) was significantly worse than in the PNI High group (≥46.7). Prognosis of patients who were both TM+ and PNI Low was significantly worse than that of patients who were either TM+ or PNI Low and those who were both TM- and PNI High . Multivariate analysis indicated that combination of TM and PNI was an independent prognostic indicator. The combination of TM and PNI offers accurate information about a patient's prognosis.

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma.

PubMed

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-11-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II-III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma

PubMed Central

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-01-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II–III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of

Prognostic and predictive potential molecular biomarkers in colon cancer.

PubMed

Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

2011-01-01

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

PubMed

Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection.

PubMed

Kuroda, Daisuke; Sawayama, Hiroshi; Kurashige, Junji; Iwatsuki, Masaaki; Eto, Tsugio; Tokunaga, Ryuma; Kitano, Yuki; Yamamura, Kensuke; Ouchi, Mayuko; Nakamura, Kenichi; Baba, Yoshifumi; Sakamoto, Yasuo; Yamashita, Yoichi; Yoshida, Naoya; Chikamoto, Akira; Baba, Hideo

2018-03-01

Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis.

PubMed

St Romain, Paul; Madan, Rashna; Tawfik, Ossama W; Damjanov, Ivan; Fan, Fang

2012-03-01

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Immunization-based scores as independent prognostic predictors in soft tissue sarcoma patients

PubMed Central

Jiang, Shan-Shan; Jiang, Long; Weng, De-Sheng; Li, Yuan-fang; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Zhou, Zhi-Wei; Xia, Jian-Chuan

2017-01-01

Background: The purpose of this study was to examine and compare the prognostic value of different immunization-based scoring systems in patients with soft tissue sarcoma (STS). Methods: We conducted a retrospective study evaluating a cohort of 165 patients diagnosed with STS between July 2007 and July 2014. The relative Glasgow prognostic score (GPS) of these patients was calculated using 3 different systems: the traditional GPS system (tGPS), the modified GPS system 1 (m1GPS), and the modified GPS system 2 (m2GPS). Then, we evaluated the relationships between each GPS system and clinicopathological characteristics. The mean follow-up for survivors in the cohort was 73.7 months as of March 2015. Results: The most favorable overall survival (OS) rate was associated with the score 0 groups, and the poorest progression-free survival (PFS) rate was associated with the score 2 groups, regardless of which system was used to calculate the score. Specifically, the m1GPS provided the greatest accuracy in predicting OS and PFS. Moreover, the same effect was observed in a separate analysis restricted to patients with metastases. Remarkably, in patients with a score of 2 as measured by all 3 systems, local treatment resulted in a poorer prognosis compared to patients with a score of 2 who did not receive local treatment. Conclusion: The GPS is a valuable prognostic marker and has the capability to predict the appropriate treatment strategy for STS patients with metastases. The modified GPS systems demonstrated superior prognostic and predictive value compared with the traditional GPS system. PMID:28367240

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

PubMed

Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

2007-11-08

Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

PubMed

Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

2014-04-01

Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

Albumin as a prognostic marker for ulcerative colitis

PubMed Central

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Trivedi, Chinmay; Yang, Yu-Xiao

2017-01-01

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis. PMID:29259376

The Evolution of Prognostic Factors in Multiple Myeloma

PubMed Central

Hassanein, Mona; Rasheed, Walid; Aljurf, Mahmoud; Alsharif, Fahad

2017-01-01

Multiple myeloma (MM) is a heterogeneous hematologic malignancy involving the proliferation of plasma cells derived by different genetic events contributing to the development, progression, and prognosis of this disease. Despite improvement in treatment strategies of MM over the last decade, the disease remains incurable. All efforts are currently focused on understanding the prognostic markers of the disease hoping to incorporate the new therapeutic modalities to convert the disease into curable one. We present this comprehensive review to summarize the current standard prognostic markers used in MM along with novel techniques that are still in development and highlight their implications in current clinical practice. PMID:28321258

Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non-curative Surgery.

PubMed

Mimatsu, Kenji; Fukino, Nobutada; Ogasawara, Yasuo; Saino, Yoko; Oida, Takatsugu

2017-08-01

The present study aimed to compare the utility of various inflammatory marker- and nutritional status-based prognostic factors, including many previous established prognostic factors, for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. A total of 33 patients with stage IV gastric cancer who had undergone palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationships between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors and cancer-specific survival (CS). Among patients who received non-curative surgery, univariate analysis of CS identified the following significant risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that the mGPS was independently associated with CS. The mGPS was a more useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing non-curative surgery for stage IV gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Machine learning classification with confidence: application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression.

PubMed

Nouretdinov, Ilia; Costafreda, Sergi G; Gammerman, Alexander; Chervonenkis, Alexey; Vovk, Vladimir; Vapnik, Vladimir; Fu, Cynthia H Y

2011-05-15

There is rapidly accumulating evidence that the application of machine learning classification to neuroimaging measurements may be valuable for the development of diagnostic and prognostic prediction tools in psychiatry. However, current methods do not produce a measure of the reliability of the predictions. Knowing the risk of the error associated with a given prediction is essential for the development of neuroimaging-based clinical tools. We propose a general probabilistic classification method to produce measures of confidence for magnetic resonance imaging (MRI) data. We describe the application of transductive conformal predictor (TCP) to MRI images. TCP generates the most likely prediction and a valid measure of confidence, as well as the set of all possible predictions for a given confidence level. We present the theoretical motivation for TCP, and we have applied TCP to structural and functional MRI data in patients and healthy controls to investigate diagnostic and prognostic prediction in depression. We verify that TCP predictions are as accurate as those obtained with more standard machine learning methods, such as support vector machine, while providing the additional benefit of a valid measure of confidence for each prediction. Copyright © 2010 Elsevier Inc. All rights reserved.

Clinicopathological significance and prognostic value of myoinvasive patterns in endometrial endometrioid carcinoma.

PubMed

Amălinei, Cornelia; Aignătoaei, Anda Maria; Balan, Raluca Anca; Giuşcă, Simona Eliza; Lozneanu, Ludmila; Avădănei, Elena Roxana; Căruntu, Irina Draga

2018-01-01

Endometrioid endometrial carcinoma has an overall good prognosis. However, variable five-year survival rates (92%-42%) have been reported in FIGO stage I, suggesting the involvement of other factors related to tumor biological behavior. These may be related to the role played by epithelial-mesenchymal transition (EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our review highlights the prognostic significance of several types of myoinvasion in low grade, low stage endometrioid endometrial carcinoma, as a reflection of these molecular changes at the invasive front. According to recently introduced myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and fragmented (MELF) patterns show loss of hormone receptors, along with EMT and high expression of cancer stem cell markers, being associated with a poor prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular invasion and lymph node metastases. Conversely, the broad front pattern has a good prognosis and a low expression of EMT and stem cells markers. Similarly, the adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM-like pattern must be differentiated from carcinoma invasion of AM foci, while adenoma malignum pattern creates difficulties in appreciating the depth of myoinvasion and requires differential diagnosis with other conditions. Another pattern expecting its validation and prognostic significance value is the nodular fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge of these patterns of myoinvasion may be valuable for the correct assessment of stage, may improve prognosis evaluation and may help identify molecules for future targeted therapies.

Expression of Glut-1 is a prognostic marker for oral squamous cell carcinoma patients.

PubMed

Eckert, A W; Lautner, M H W; Taubert, H; Schubert, J; Bilkenroth, U

2008-12-01

Oral squamous cell carcinoma (OSCC) is among the tenth most common human cancers worldwide with evidence of an increase in incidence rate and mortality. Despite advances in treatment modalities, the prognosis of this cancer is still very poor and has not changed over the past two decades. This study is based on samples collected from 42 patients with a primary OSCC. Immunohistochemical staining for Glut-1 was carried out and compared with the clinicopathological data. Thirty-two patients showed in their tumors a weak or undetectable Glut-1 expression, whereas in tumors of 10 patients a moderate to strong Glut-1 expression was detected. In multivariate Cox's regression hazard analysis, patients whose tumors had a moderate to strong Glut-1 expression possessed a 4.9-fold increased risk of tumor-related death compared to the other patients. Our results suggest that Glut-1 expression is an independent prognostic marker for routine assessment of OSCC.

RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

PubMed Central

Catenacci, Daniel VT; Cervantes, Gustavo; Yala, Soheil; Nelson, Erik A; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Brägelmann, Johannes; Seiwert, Tanguy; Sanicola, Michele; Henderson, Les; Grushko, Tatyana A; Olopade, Olufunmilayo; Karrison, Theodore; Bang, Yung-Jue; Ho Kim, Woo; Tretiakova, Maria; Vokes, Everett; Frank, David A; Kindler, Hedy L; Huet, Heather

2011-01-01

RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. a novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both ROn and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for

Prognostic and predictive factors in colorectal cancer.

PubMed

Bolocan, A; Ion, D; Ciocan, D N; Paduraru, D N

2012-01-01

Colorectal cancer (CRC) is an important public health problem; it is a leading cause of cancer mortality in the industrialized world, second to lung cancer: each year there are nearly one million new cases of CRC diagnosed worldwide and half a million deaths (1). This review aims to summarise the most important currently available markers for CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed by tumour tissues, such as thymidylate synthase, and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices, such as the apoptotic index, are discussed. The advent of new therapies created the pathway for a personalized approach of the patient. This will take into consideration the complex genetic mechanisms involved in tumorigenesis, besides the classical clinical and pathological stagings. The growing number of therapeutic agents and known molecular targets in oncology lead to a compulsory study of the clinical use of biomarkers with role in improving response and survival, as well as in reducing toxicity and establishing economic stability. The potential predictive and prognostic biomarkers which have arisen from the study of the genetic basis of colorectal cancer and their therapeutical significance are discussed. RevistaChirurgia.

Prognostic markers for colorectal cancer: estimating ploidy and stroma

PubMed Central

Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

2018-01-01

Abstract Background We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13–2.77) and HR = 2.95 (95% CI: 1.73–5.03), P < 0.001]. Conclusion A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals. PMID:29293881

Sleep-time BP: prognostic marker of type 2 diabetes and therapeutic target for prevention.

PubMed

Hermida, Ramón C; Ayala, Diana E; Mojón, Artemio; Fernández, José R

2016-02-01

We investigated the prognostic value of clinic and ambulatory BP (ABP) to predict new-onset diabetes and whether risk reduction is related to the progressive decrease of clinic BP or awake or asleep ABP. We prospectively evaluated 2,656 individuals without diabetes, 1,292 men and 1,364 women, 50.6 ± 14.3 years of age, with baseline BP ranging from normotension to hypertension according to ABP criteria. At baseline and annually (more frequently if hypertension treatment was adjusted based on ABP) thereafter, ABP and physical activity (wrist actigraphy) were simultaneously monitored for 48 h to accurately derive the awake and asleep BP means. During a 5.9-year median follow-up, 190 participants developed type 2 diabetes. The asleep systolic ABP mean was the most significant predictor of new-onset diabetes in a Cox proportional-hazard model adjusted for age, waist circumference, glucose, chronic kidney disease (CKD) and hypertension treatment. Daytime clinic BP and awake or 48 h ABP mean had no predictive value when corrected by the asleep ABP mean. Analyses of BP changes during follow-up revealed a 30% reduction in the risk of new-onset diabetes per 1-SD decrease in asleep systolic ABP mean, independent of changes in clinic BP or awake or 48 h ABP means. Sleep-time BP is a highly significant independent prognostic marker for new-onset diabetes. Alteration in sleep-time BP regulation seems to precede, rather than follow, the development of new-onset diabetes. Most important, lowering asleep BP, a novel therapeutic target requiring ABP evaluation, could be a significant method for reducing new-onset diabetes risk.

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

PubMed Central

Zhan, Ping; Xi, Guang-Min; Liu, Hong-Bing; Liu, Ya-Fang; Xu, Wu-Jian; Zhu, Qingqing; Zhou, Ze-Jun; Miao, Ying-Ying; Wang, Xiao-Xia; Jin, Jia-Jia

2017-01-01

Background Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. Methods PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC. PMID:28840006

The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer

PubMed Central

Ling, Agnes; Lundberg, Ida V; Eklöf, Vincy; Wikberg, Maria L; Öberg, Åke; Palmqvist, Richard

2015-01-01

Abstract Giving strong prognostic information, T‐cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T‐bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype‐high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild‐type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1‐attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T‐bet may be a valuable marker in the clinical setting. Our results also indicate that T‐bet is of

Incorporating prognostic imaging biomarkers into clinical practice

PubMed Central

Miles, Kenneth A.

2013-01-01

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

PubMed Central

Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Mei

2015-01-01

Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients. PMID:25624992

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Is Thrombocytopenia an Early Prognostic Marker in Septic Shock?

PubMed

Thiery-Antier, Nadiejda; Binquet, Christine; Vinault, Sandrine; Meziani, Ferhat; Boisramé-Helms, Julie; Quenot, Jean-Pierre

2016-04-01

To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. Prospective, multicenter, observational cohort study. Fourteen ICUs from 10 French university teaching and nonacademic hospitals. Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. None. Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p ≤ 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p < 0.0001). This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

Application of molecular biology of differentiated thyroid cancer for clinical prognostication.

PubMed

Marotta, Vincenzo; Sciammarella, Concetta; Colao, Annamaria; Faggiano, Antongiulio

2016-11-01

Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. © 2016 Society for Endocrinology.

Molecular markers in bladder cancer: Novel research frontiers.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

[Skeletal Mass Depletion Is a Negative Prognostic Factor in Gastrointestinal Cancer Patients in the Terminal Stage].

PubMed

Takahashi, Goro; Yamada, Takeshi; Kan, Hayato; Koizumi, Michihiro; Shinji, Seiichi; Yokoyama, Yasuyuki; Iwai, Takuma; Uchida, Eiji

2015-10-01

Skeletal mass depletion has been reported to be a prognostic factor for cancer patients. However, special and expensive devices are required to measure skeletal mass, and this is a major reason why skeletal mass is not used extensively for prognostic marker in clinical settings. We developed a new method to measure skeletal mass for use as a prognostic marker using CT images without special and expensive devices. In this study, we evaluated the usefulness of skeletal mass as measured by this new method as a prognostic marker for gastrointestinal cancer patients. Patients who died from gastrointestinal cancer between March 2010 and October 2013 were included. We measured the right-sided maximum psoas muscle cross sectional area (MPCA) by using CT images before surgery and after the patients developed a terminal condition. The maximum psoas muscle cross sectional area ratio (MPCA-R) was defined as follows: MPCA-R=MPCA before surgery/MPCA after developing a terminal condition. We evaluated the correlation between MPCA-R and survival. Fifty-nine patients were included. The median survival was 44 days, and MPCA-R was significantly correlated with survival (p=0.001). On receiver operating characteristic (ROC) analysis, the area under the curve (AUC) to predict 30-day and 90-day survival was 0.710 and 0.748, respectively. MPCA-R is a new and novel prognostic marker for gastrointestinal cancer patients in terminal condition.

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients.

PubMed

Geboers, Diederik G P J; de Beer, Friso M; Tuip-de Boer, Anita M; van der Poll, Tom; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J M; Ong, David S Y; Schultz, Marcus J; Bos, Lieuwe D J

2015-07-01

We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. suPAR was determined batchwise in plasma obtained within 24 h after admission. 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1-15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5-16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P < 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29%), SOFA score (23%), OI (38%), and Berlin definition classification (39%). As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies

PubMed Central

2012-01-01

Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review. PMID:22857649

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

PubMed

Lin, Yao; Shen, Lu-Yan; Fu, Hao; Dong, Bin; Yang, He-Li; Yan, Wan-Pu; Kang, Xiao-Zheng; Dai, Liang; Zhou, Hai-Tao; Yang, Yong-Bo; Liang, Zhen; Chen, Ke-Neng

2017-02-01

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future. © 2016 International Society for Diseases of the Esophagus.

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Microsatellite markers from the 'South American fruit fly' Anastrepha fraterculus: a valuable tool for population genetic analysis and SIT applications

PubMed Central

2014-01-01

Background Anastrepha fraterculus Wiedemann is a horticultural pest which causes significant economic losses in the fruit-producing areas of the American continent and limits the access of products to international markets. The use of environmentally friendly control strategies against this pest is constrained due to the limited knowledge of its population structure. Results We developed microsatellite markers for A. fraterculus from four genomic libraries, which were enriched in CA, CAA, GA and CAT microsatellite motifs. Fifty microsatellite regions were evaluated and 14 loci were selected for population genetics studies. Genotypes of 122 individuals sampled from four A. fraterculus populations were analyzed. The level of polymorphism ranged from three to 13 alleles per locus and the mean expected heterozygosity ranged from 0.60 to 0.64. Comparison between allelic and genotypic frequencies showed significant differences among all pairs of populations. Conclusions This novel set of microsatellite markers provides valuable information for the description of genetic variability and population structure of wild populations and laboratory strains of A. fraterculus. This information will be used to identify and characterize candidate strains suitable to implement effective pest control strategies and might represent a first step towards having a more comprehensive knowledge about the genetics of this pest. PMID:25471285

Improving the Prognostic Ability through Better Use of Standard Clinical Data - The Nottingham Prognostic Index as an Example

PubMed Central

Winzer, Klaus-Jürgen; Buchholz, Anika; Schumacher, Martin; Sauerbrei, Willi

2016-01-01

Background Prognostic factors and prognostic models play a key role in medical research and patient management. The Nottingham Prognostic Index (NPI) is a well-established prognostic classification scheme for patients with breast cancer. In a very simple way, it combines the information from tumor size, lymph node stage and tumor grade. For the resulting index cutpoints are proposed to classify it into three to six groups with different prognosis. As not all prognostic information from the three and other standard factors is used, we will consider improvement of the prognostic ability using suitable analysis approaches. Methods and Findings Reanalyzing overall survival data of 1560 patients from a clinical database by using multivariable fractional polynomials and further modern statistical methods we illustrate suitable multivariable modelling and methods to derive and assess the prognostic ability of an index. Using a REMARK type profile we summarize relevant steps of the analysis. Adding the information from hormonal receptor status and using the full information from the three NPI components, specifically concerning the number of positive lymph nodes, an extended NPI with improved prognostic ability is derived. Conclusions The prognostic ability of even one of the best established prognostic index in medicine can be improved by using suitable statistical methodology to extract the full information from standard clinical data. This extended version of the NPI can serve as a benchmark to assess the added value of new information, ranging from a new single clinical marker to a derived index from omics data. An established benchmark would also help to harmonize the statistical analyses of such studies and protect against the propagation of many false promises concerning the prognostic value of new measurements. Statistical methods used are generally available and can be used for similar analyses in other diseases. PMID:26938061

[Expression of BAG3 Gene in Acute Myeloid Leukemia and Its Prognostic Value].

PubMed

Zhu, Hua-Yuan; Fu, Yuan; Wu, Wei; Xu, Jia-Dai; Chen, Ting-Mei; Qiao, Chun; Li, Jian-Yong; Liu, Peng

2015-08-01

To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value. Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed. In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients. The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.

Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

PubMed

Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

2015-03-01

Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer.

PubMed

Dunne, Philip D; Dasgupta, Sonali; Blayney, Jaine K; McArt, Darragh G; Redmond, Keara L; Weir, Jessica-Anne; Bradley, Conor A; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H; Johnston, Patrick G; Van Schaeybroeck, Sandra

2016-01-01

EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear. EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models. Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells. These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. ©2015 American Association for Cancer Research.

EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer

PubMed Central

Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.

2015-01-01

Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684

Prognostic value of biological markers in myocardial infarction patients.

PubMed

Berezin, Alexander E; Samura, Tatiana A

2013-04-01

The aim of this study was to compare the prognostic value of matrix metalloproteinase-3 and -9, and NT-pro-natriuretic peptide for fatal and nonfatal complications in Q-wave myocardial infarction patients in the acute and postinfarction periods. 85 men and women with documented Q-wave myocardial infarction were observed for 1 year after hospitalization. Clinical endpoints were identified through the hospital patient-tracking system, with a review of medical records for each recorded endpoint. Left ventricular ejection fraction and wall motion index were calculated. Measurements of matrix metalloproteinases and NT-pro-natriuretic peptide were performed by an enzyme-linked immunosorbent assay. A cutoff value of 9.7 ng·mL(-1) for matrix metalloproteinase-3 showed the best discriminatory power (sensitivity = 77.8%, specificity = 90.8%). The optimal cutoff value of matrix metalloproteinase-9 was 18.1 ng·mL(-1) (sensitivity, 70.5%; specificity, 75%), and the cutoff for NT-pro-natriuretic peptide was 885 pmol·L(-1) (sensitivity, 58%; specificity, 68.6%). Matrix metalloproteinase-3 and -9 were strongly related with a positive prognostic value of 70% (sensitivity and specificity, 84% and 82%, respectively). These data may be helpful for further stratification of patients into cardiovascular mortality risk groups.

Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma.

PubMed

Turner, J R; Torres, C M; Wang, H H; Shahsafaei, A; Richards, W G; Sugarbaker, D; Odze, R D

2000-03-01

BAd. Thus, the prognostic utility of ECAD expression must be evaluated in the context of chemrad status. CD44 also may be a valuable prognostic marker in BAd.

Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

PubMed

Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

2001-01-01

Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

PubMed Central

Xavier-Magalhães, Ana; Gonçalves, Céline S.; Fogli, Anne; Lourenço, Tatiana; Pojo, Marta; Pereira, Bruno; Rocha, Miguel; Lopes, Maria Celeste; Crespo, Inês; Rebelo, Olinda; Tão, Herminio; Lima, João; Moreira, Ricardo; Pinto, Afonso A.; Jones, Chris; Reis, Rui M.; Costello, Joseph F.; Arnaud, Philippe; Sousa, Nuno; Costa, Bruno M.

2018-01-01

The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2′-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer. PMID:29644006

Clinicopathologic and prognostic implications of progranulin in breast carcinoma.

PubMed

Li, Li-qin; Huang, Hui-lian; Ping, Jin-liang; Wang, Xiao-hong; Zhong, Jing; Dai, Li-cheng

2011-07-05

Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. Its expression is closely correlated with the development and metastasis of several cancers. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathologic features in breast carcinoma biopsies, and the role of progranulin as a new marker of metastatic risk and prognosis in breast cancer has not yet been studied. The aim of this study was to investigate the clinicopathologic and prognostic implications of progranulin expression in breast carcinoma and its correlation with tumor angiogenesis. Progranulin expression was determined immunohistochemically in 183 surgical specimens from patients with breast cancer and 20 tissue samples from breast fibroadenomas. The tumor angiogenesis-related biomarker, vascular endothelial growth factor was assayed and microvessel density was assessed by counting vascular endothelial cells in tumor tissues labeled with endoglin antibody. The relationship between progranulin expression and the clinicopathologic data were analyzed. Progranulin proteins were overexpressed in breast cancer. The level of progranulin expression was significantly correlated with tumor size (P = 0.004), lymph node metastasis (P < 0.001) and TNM staging (P < 0.001). High progranulin expression was associated with higher tumor angiogenesis, reflected by increased vascular endothelial growth factor expression (P < 0.001) and higher microvessel density (P = 0.002). Progranulin may be a valuable marker for assessing the metastasis and prognosis of breast cancer, and could provide the basis for new combination regimens with antiangiogenic activity.

Prognostic value of mitotic counts in breast cancer of Saudi Arabian patients.

PubMed

Buhmeida, Abdelbaset; Al-Maghrabi, Jaudah; Merdad, Adnan; Al-Thubaity, Fatima; Chaudhary, Adeel; Gari, Mamdooh; Abuzenadah, Adel; Collan, Yrjö; Syrjänen, Kari; Al-Qahtani, Mohammed

2011-01-01

Quantitative methods in combination with other objective prognostic criteria can improve the evaluation of a cancer patient's prognosis, and possibly predict response to therapy. One of the important prognostic and predictive markers is the mitotic count, which has proven valuable in many aspects. In this study, the prognostic value of the mitotic count was assessed in breast cancer (BC) patients in Saudi Arabia. The study comprised a series of 87 patients diagnosed and treated for breast cancer at the Departments of Surgery and Oncology, King Abdul-Aziz University Hospital, between 2000 and 2008. Mitotic counts were carried out using a standard laboratory microscope (objective, × 40; field diameter, 420 μm). The number of mitotic figures in 10 consecutive high-power fields (hpf) from the most cellular area of the sample gave the mitotic activity index (MAI, mitotic figures/10 hpf). The standardized mitotic index (SMI) recorded the mitotic count as the number of mitotic figures by area of the neoplastic tissue in the microscopic field, thus the number of mitoses in 10 consecutive fields was corrected for the volume fraction and field size (mitotic figures/mm²). The means of MAI and SMI of the tumors in the entire series of 87 patients were 15 mitotic figures/10 hpf (range 4-45) and 4 mitotic figures/mm² (range 1-9), respectively. The mitotic counts were higher in advanced stages than in early cancer (p < 0.04). The mitotic counts were significantly larger in patients with high-grade tumor (p < 0.004) and in cases with tumor metastasis (p < 0.004). The mitotic counts were also significantly larger in the recurrent cases than in non-recurrent ones (p < 0.02). The quantitatively measurable mitotic counts of cancer cell nuclei are of significant prognostic value in invasive ductal carcinoma of the breast in Saudi Arabia and the mean cut-off values of MAI and SMI can be applied as objective (quantitative) criteria to distinguish breast cancer patients into groups

Bim is an Independent Prognostic Marker in Intrahepatic Cholangiocarcinoma.

PubMed

Zhang, Henan; Jenkins, Sarah M; Lee, Chuang-Ta; Harrington, Susan M; Liu, Zhuogang; Dong, Haidong; Zhang, Lizhi

2018-04-23

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignant tumor and has a poor prognosis. The prognostic factors associated with outcome remain poorly defined. In this study, we investigated the role of an important cell apoptosis initiator, Bcl-2 interacting mediator of cell death (Bim), by evaluating its expression and association with other clinicopathologic features in ICCs. We analyzed 56 cases of ICC with clinical follow-up. The expression of Bim in ICC cells and other cellular components was evaluated by immunohistochemistry. Bim expression was considered upregulated if Bim was detected in 10% or more of tumor cells. Of the 56 ICC samples, 19 (34%) had high Bim expression level, 15 (27%) were completely negative, and 22 (39%) were classified as low Bim expression (<10% positivity). Patients who had tumors with high Bim level had significantly longer overall survival than those with low or no staining (median survival, 7.6 vs 2.6 years; hazard ratio, 0.40; P=.006). High Bim expression was also correlated with low Ki-67 index, and more importantly, none of the tumors with high Bim expression had lymph node metastases at the time of surgery. Our study demonstrates that Bim is an important and independent prognostic factor in ICC. Tumors with high Bim expression are associated with better prognosis through inhibiting tumor cell proliferation and metastatic ability. The development of new agents directly or indirectly targeting Bim may provide promising anticancer treatments. Copyright © 2018. Published by Elsevier Inc.

Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women's Cancers.

PubMed

Bartlett, Thomas E; Jones, Allison; Goode, Ellen L; Fridley, Brooke L; Cunningham, Julie M; Berns, Els M J J; Wik, Elisabeth; Salvesen, Helga B; Davidson, Ben; Trope, Claes G; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

2015-01-01

We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.

ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma.

PubMed

Pieraccioli, Marco; Nicolai, Sara; Pitolli, Consuelo; Agostini, Massimiliano; Antonov, Alexey; Malewicz, Michal; Knight, Richard A; Raschellà, Giuseppe; Melino, Gerry

2018-06-25

Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB. Copyright © 2018 the Author(s). Published by PNAS.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Chromogranin A and neuron-specific enolase in neuroblastoma: Correlation to stage and prognostic factors.

PubMed

Georgantzi, Kleopatra; Sköldenberg, Erik G; Stridsberg, Mats; Kogner, Per; Jakobson, Åke; Janson, Eva Tiensuu; Christofferson, Rolf H B

2018-05-08

Chromogranin A (CgA) and neuron specific enolase (NSE) are important markers in adult neuroendocrine tumors (NET). Neuroblastoma (NB) has certain neuroendocrine properties. The aim of this study was to correlate blood concentrations of CgA, chromogranin B (CgB), and NSE to prognostic factors and outcome in children with NB. Blood samples from 92 patients with NB, 12 patients with benign ganglioneuroma (GN), 21 patients with non-NB solid tumors, 10 patients with acute leukemias, and 69 healthy children, were analyzed. CgA concentrations were higher in neonates vs. children older than one month in the control group (p < 0.0001), and in neonates with NB vs. the control group (p < 0.01). CgA and NSE concentrations were higher in patients with stages 3 and 4 disease (p < 0.05 and p < 0.05), in patients having tumors with amplification of MYCN (p < 0.05 and p < 0.001), or chromosome 1 p deletion (p < 0.05 and p < 0.05). NSE correlated to the tumor size at diagnosis (p < 0.001) and to tumor related death (p < 0.01) in NB. CgA and NSE concentrations were elevated in patients with NB and especially in those with advanced disease. Both CgA and NSE correlated to genetic markers, while only NSE correlated to primary tumor size and outcome in NB. We found that CgA and NSE are clinically valuable tumor markers in NB and they merit prospective clinical evaluations as such.

Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission

PubMed Central

Herbeck, Joshua T.; Müller, Viktor; Maust, Brandon S.; Ledergerber, Bruno; Torti, Carlo; Di Giambenedetto, Simona; Gras, Luuk; Günthard, Huldrych F.; Jacobson, Lisa P.; Mullins, James I.; Gottlieb, Geoffrey S.

2013-01-01

Objective The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results. Design We conducted a meta-analysis of changes in baseline CD4+ T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence. Methods We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4+ T-cell counts (21 052 total individuals), and eight studies of trends in set point viral loads (10 785 total individuals), spanning the years 1984–2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4+ T-cell counts. Results Baseline CD4+ T-cell counts showed a summary trend of decreasing cell counts [effect=−4.93 cells/µl per year, 95% confidence interval (CI) −6.53 to −3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect=0.013 log10 copies/ml per year, 95% CI −0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. Conclusion Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4+ T cells loss of approximately 148 cells/µl and a gain of 0.39 log10 copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk. PMID:22089381

Diagnostic, prognostic and predictive relevance of molecular markers in gliomas.

PubMed

Brandner, Sebastian; von Deimling, Andreas

2015-10-01

The advances of genome-wide 'discovery platforms' and the increasing affordability of the analysis of significant sample sizes have led to the identification of novel mutations in brain tumours that became diagnostically and prognostically relevant. The development of mutation-specific antibodies has facilitated the introduction of these convenient biomarkers into most neuropathology laboratories and has changed our approach to brain tumour diagnostics. However, tissue diagnosis will remain an essential first step for the correct stratification for subsequent molecular tests, and the combined interpretation of the molecular and tissue diagnosis ideally remains with the neuropathologist. This overview will help our understanding of the pathobiology of common intrinsic brain tumours in adults and help guiding which molecular tests can supplement and refine the tissue diagnosis of the most common adult intrinsic brain tumours. This article will discuss the relevance of 1p/19q codeletions, IDH1/2 mutations, BRAF V600E and BRAF fusion mutations, more recently discovered mutations in ATRX, H3F3A, TERT, CIC and FUBP1, for diagnosis, prognostication and predictive testing. In a tumour-specific topic, the role of mitogen-activated protein kinase pathway mutations in the pathogenesis of pilocytic astrocytomas will be covered. © 2015 British Neuropathological Society.

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer

PubMed Central

Blok, Erik J.; van den Bulk, Jitske; Dekker-Ensink, N. Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.

2017-01-01

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression. PMID:28121628

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer.

PubMed

Blok, Erik J; van den Bulk, Jitske; Dekker-Ensink, N Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R; van de Velde, Cornelis J H; Kuppen, Peter J K

2017-02-28

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression.

Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.

PubMed

Kahlert, Christoph; Fiala, Maria; Musso, Gabriel; Halama, Niels; Keim, Sophia; Mazzone, Massimiliano; Lasitschka, Felix; Pecqueux, Mathieu; Klupp, Fee; Schmidt, Thomas; Rahbari, Nuh; Schölch, Sebastian; Pilarsky, Christian; Ulrich, Alexis; Schneider, Martin; Weitz, Juergen; Koch, Moritz

2014-12-30

Pancreatic cancer consists of a heterogenous bulk of tumor cells and stroma cells which contribute to tumor progression by releasing angiogenic factors. Those factors can be detected as circulating serum factors. We performed a compartment-specific analysis of tumor-derived and stroma-derived angiogenic factors to identify biomarkers and molecular targets for the treatment of pancreatic cancer. Kryo-frozen tissue from primary ductal adenocarcinomas (n = 51) was laser-microdissected to isolate tumor and stroma tissue. Expression of 17 angiogenic factors (angiopoietin-2, follistatin, GCSF, HGF, interleukin-8, leptin, PDGF-BB, PECAM-1, VEGF, matrix metalloproteinase -1, -2, -3, -7, -9, -10, -12, and -13) was analyzed using a multiplex elisa assay for tissue-derived proteins and corresponding serum. Our study reveals a compartment-specific expression profile for several angiogenic factors and matrix metalloproteinases. ROC analysis of corresponding serum samples reveals MMP-7 and MMP-12 as strong classifiers for the diagnosis of patients with pancreatic cancer vs. healthy control donors. High expression of tumor-derived PDGF-BB and MMP-1 correlates with prolonged survival in univariate and multivariate analysis. In conclusion, a distinct expression patterns for angiogenic cytokines and MMPs in pancreatic cancer and surrounding stroma may implicate them as novel targets for cancer treatment. Tumor-derived PDGF-BB and MMP-1 are significant and independent prognostic markers for poor survival.

Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes

PubMed Central

Roy, Janine; Aust, Daniela; Knösel, Thomas; Rümmele, Petra; Jahnke, Beatrix; Hentrich, Vera; Rückert, Felix; Niedergethmann, Marco; Weichert, Wilko; Bahra, Marcus; Schlitt, Hans J.; Settmacher, Utz; Friess, Helmut; Büchler, Markus; Saeger, Hans-Detlev; Schroeder, Michael; Pilarsky, Christian; Grützmann, Robert

2012-01-01

Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice. PMID:22615549

BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.

PubMed

Yin, Guozhi; Liu, Zhikui; Wang, Yufeng; Dou, Changwei; Li, Chao; Yang, Wei; Yao, Yingmin; Liu, Qingguang; Tu, Kangsheng

2016-02-15

The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

Old, New, and Emerging Immunohistochemical Markers in Pheochromocytoma and Paraganglioma.

PubMed

Cheung, Veronica K Y; Gill, Anthony J; Chou, Angela

2018-05-19

The evolution of genetic research over the past two decades has greatly improved the understanding of pheochromocytomas and paragangliomas. It is now accepted that more than one third of pheochromocytoma and paragangliomas arise in the context of syndromic disease, usually hereditary. The genetic profile of these tumors also has important prognostic implications which may help guide treatment. Accompanying the changing molecular landscape is the development of new immunohistochemical markers. Initially used in assisting with diagnosis, immunohistochemical markers have now become an important adjunct to screening programs for inherited conditions and subsequently as prognostic markers. The accessibility and efficiency of immunohistochemistry bring pathologists to the forefront in triaging patients based on tumor genotype-phenotype. In this review, we provide an update on the role of immunohistochemistry in the diagnosis of pheochromocytomas and paragangliomas, as an adjunct to assessment for hereditary disease and finally as a potential tool to assist risk stratification.

Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer.

PubMed

Wikberg, Maria L; Ling, Agnes; Li, Xingru; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

2017-10-01

The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC. The infiltration of CD66b-positive cells was semi-quantitatively evaluated along the tumor invasive front, in the tumor center, and within the tumor epithelium (intraepithelial expression). We found that poor infiltration of CD66b-positive cells in the tumor front indicated a worse patient prognosis. The prognostic significance of CD66b infiltration was found to be mainly independent of tumor molecular characteristics and maintained significance in multivariable analysis of stage I-II colon cancers. We further analyzed the prognostic impact of CD66b-positive cells in relation to other immune markers (NOS2, CD163, Tbet, FOXP3, and CD8) and found that neutrophil infiltration, even though strongly correlated to infiltration of other immune cell subsets, had additional prognostic value. In conclusion, we find that low infiltration of neutrophils in the tumor front is an independent prognostic factor for a poorer patient prognosis in early stages of colon cancers. Further studies are needed to elucidate the biological role of neutrophils in colorectal carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women’s Cancers

PubMed Central

Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Berns, Els M. J. J.; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

2015-01-01

We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes. PMID:26629914

A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.

PubMed

Hayıroğlu, Mert İlker; Keskin, Muhammed; Keskin, Taha; Uzun, Ahmet Okan; Altay, Servet; Kaya, Adnan; Öz, Ahmet; Çinier, Göksel; Güvenç, Tolga Sinan; Kozan, Ömer

2018-05-01

The prognostic impact of nutritional status in patients with pulmonary embolism (PE) is poorly understood. A well-accepted nutritional status parameter, prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and gastrointestinal surgery, was introduced to patients with PE. Our aim was to evaluate the predictive value of PNI in outcomes of patients with PE. We evaluated the in-hospital and long-term (53.8 ± 5.4 months) prognostic impact of PNI on 251 patients with PE. During a median follow-up of 53.8 ± 5.4 months, 27 (11.6%) patients died in hospital course and 31 (13.4%) died in out-of-hospital course. The patients with lower PNI had significantly higher in-hospital and long-term mortality. The Cox proportional hazard analyses showed that PNI was associated with an increased risk of all-cause death for both unadjusted model and adjusted for all covariates. Our study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with PE.

Prognostic nomogram for previously untreated adult patients with acute myeloid leukemia

PubMed Central

Zheng, Zhuojun; Li, Xiaodong; Zhu, Yuandong; Gu, Weiying; Xie, Xiaobao; Jiang, Jingting

2016-01-01

This study was designed to perform an acceptable prognostic nomogram for acute myeloid leukemia. The clinical data from 311 patients from our institution and 165 patients generated with Cancer Genome Atlas Research Network were reviewed. A prognostic nomogram was designed according to the Cox's proportional hazard model to predict overall survival (OS). To compare the capacity of the nomogram with that of the current prognostic system, the concordance index (C-index) was used to validate the accuracy as well as the calibration curve. The nomogram included 6 valuable variables: age, risk stratifications based on cytogenetic abnormalities, status of FLT3-ITD mutation, status of NPM1 mutation, expression of CD34, and expression of HLA-DR. The C-indexes were 0.71 and 0.68 in the primary and validation cohort respectively, which were superior to the predictive capacity of the current prognostic systems in both cohorts. The nomogram allowed both patients with acute myeloid leukemia and physicians to make prediction of OS individually prior to treatment. PMID:27689396

Ulex europeus agglutinin-I binding as a potential prognostic marker in ovarian cancer.

PubMed

Blonski, Katharina; Milde-Langosch, Karin; Bamberger, Ana-Maria; Osterholz, Tina; Utler, Christian; Berger, Jürgen; Löning, Thomas; Schumacher, Udo

2007-01-01

Ovarian cancer represents the malignant tumour of the female genital tract with the worst prognosis, mainly caused by early intraperitoneal spread. Cell-to-cell and cell-to-matrix interactions play a functionally important role in this spread and are both mediated by the cell membrane. Changes in the glycosylation of the cell membrane, as detected by lectin histochemistry, are sometimes associated with a poor prognosis. The expression of lectin binding of 164 ovarian cancer patients was analysed and the staining results were correlated with the clinical data of the patients. The univariate and multivariate statistical analysis revealed an independent prognostic significance for Ulex europeus agglutinin-I (UEA-I) binding. These findings indicate that UEA-I binding can serve as a prognostic factor in ovarian cancer.

Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients.

PubMed

Johnbeck, Camilla B; Knigge, Ulrich; Langer, Seppo W; Loft, Annika; Berthelsen, Anne Kiil; Federspiel, Birgitte; Binderup, Tina; Kjaer, Andreas

2016-12-01

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18 F-FLT PET as a prognostic marker for NENs in comparison with 18 F-FDG PET and Ki-67 index. One hundred patients were PET-scanned with both 18 F-FLT and 18 F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18 F-FLT uptake was also investigated. Thirty-seven percent of patients had a positive 18 F-FLT PET scan, and 49% had 18 F-FDG PET-positive foci. Patients with a high 18 F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18 F-FLT uptake. No correlation was found between Ki-67 index and 18 F-FLT uptake. In a multivariate analysis 18 F-FLT, 18 F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18 F-FDG and Ki-67 remained significant. 18 F-FLT PET has prognostic value in NEN patients but when 18 F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18 F-FLT PET only adds information regarding PFS but not OS, whereas 18 F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18 F-FLT in addition to 18 F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18 F-FLT PET in NENs remains to be established. © 2016 by the Society of Nuclear Medicine and Molecular

Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications

PubMed Central

Berretta, Massimiliano; Cavaliere, Carla; Facchini, Gaetano; Balestreri, Luca; Perin, Tiziana; Canzonieri, Vincenzo

2017-01-01

HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument. PMID:28077782

Anti-Műllerian hormone – a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome

PubMed Central

Neagu, M; Cristescu, C

2012-01-01

Background: The anti- Műllerian hormone (AMH) is secreted in women exclusively by the granulosa cells of the ovarian follicles. The serum level of AMH is a precise marker of follicle pool size. In recent clinical studies of polycystic ovary syndrome (PCOS), the serum levels of AMH were elevated about two to threefold. The use of metformin in women with infertility and PCOS has proved to be efficient: restoring ovulation and reducing metabolic dysfunctions. The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS). Methods: Eleven patients with infertility and PCOS were enrolled; PCOS was diagnosed according to the criteria of Androgen Excess and Polycystic Ovarian Syndrome Society 2006 (AE/PCOS). All patients have received metformin therapy. Serum AMH was recorded before and after 2 months of treatment; the normal laboratory values were 2.0-6.8 ng/ml. Results: The primary serum AMH level of all women in study was very high: 8.99±0.99 ng/ml. After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased. Conclusions: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency. PMID:23346251

Prognostic value of vitamin D level for all-cause mortality, and association with inflammatory markers, in HIV-infected persons.

PubMed

Shepherd, Leah; Souberbielle, Jean-Claude; Bastard, Jean-Philippe; Fellahi, Soraya; Capeau, Jaqueline; Reekie, Joanne; Reiss, Peter; Blaxhult, Anders; Bickel, Markus; Leen, Clifford; Kirk, Ole; Lundgren, Jens D; Mocroft, Amanda; Viard, Jean-Paul

2014-07-15

Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

PubMed

Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; Arenillas, Leonor; Valcarcel, David; Vallespí, Teresa; Costa, Dolors; Nomdedeu, Benet; Jimenez, María José; Granada, Isabel; Grau, Javier; Ardanaz, María T; de la Serna, Javier; Carbonell, Félix; Cervera, José; Sierra, Adriana; Luño, Elisa; Cervero, Carlos J; Falantes, José; Calasanz, María J; González-Porrás, José R; Bailén, Alicia; Amigo, M Luz; Sanz, Guillermo; Solé, Francesc

2013-07-01

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prognostic Value of Risk Score and Urinary Markers in Idiopathic Membranous Nephropathy

PubMed Central

Hofstra, Julia M.; Wetzels, Jack F.M.

2012-01-01

Summary Background and objectives Accurate prediction of prognosis may improve management of patients with idiopathic membranous nephropathy. This study compared the Toronto Risk Score and urinary low-molecular weight proteins. Design, setting, participants, & measurements One hundred four patients with biopsy-proven idiopathic membranous nephropathy who presented between 1995 and 2008 with a well-preserved kidney function and nephrotic range proteinuria were included. Urinary β2-microglobulin and α1-microglobulin measurements were obtained by timed standardized measurements, and the Toronto Risk Score was calculated using data obtained from medical records. The endpoint was progression, which was defined as an increase in serum creatinine>50% or >25% with a concentration>135 μmol/L. Results Forty-nine patients showed progression. The area under the receiver-operating characteristics curve was 0.78 (95% confidence interval=0.69–0.88) for the risk score versus 0.80 (0.71–0.89) and 0.79 (0.71–0.88) for urinary β2- and α1-microglobulin, respectively. Differences were not significant. Persistent proteinuria did not add accuracy to the Toronto Risk Score. Conversely, its accuracy was not reduced when data from the first 6 months of follow-up were used. Furthermore, a score based on GFR estimated with the six-variable Modification of Diet in Renal Disease equation, calculated in the first 6 months of follow-up, gave an area under the receiver-operating characteristics curve of 0.83 (0.74–0.92), which was not statistically different from other markers. Conclusions The prognostic accuracies of the Toronto Risk Score and urinary low-molecular weight proteins were not significantly different. The risk score can be calculated within 6 months of diagnosis, and a simplified risk score using estimated GFR–Modification of Diet in Renal Disease may be sufficient. PMID:22595828

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.

PubMed

van Rhijn, Bas W G; Catto, James W; Goebell, Peter J; Knüchel, Ruth; Shariat, Shahrokh F; van der Poel, Henk G; Sanchez-Carbayo, Marta; Thalmann, George N; Schmitz-Dräger, Bernd J; Kiemeney, Lambertus A

2014-10-01

To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study.

PubMed

Morgenthaler, Nils G; Struck, Joachim; Christ-Crain, Mirjam; Bergmann, Andreas; Müller, Beat

2005-02-01

Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

Prognostic value of Child-Turcotte criteria in medically treated cirrhosis.

PubMed

Christensen, E; Schlichting, P; Fauerholdt, L; Gluud, C; Andersen, P K; Juhl, E; Poulsen, H; Tygstrup, N

1984-01-01

The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A----B----C) of albumin (p less than 0.001), ascites (p less than 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.

Family Type as a Prognostic Indicator of Rehabilitation Outcome with Post-Hospitalized Male Schizophrenics

ERIC Educational Resources Information Center

Beres, Barbara Oliver; Frumkin, Robert M.

1973-01-01

A study of 65 male schizophrenic patients at the Bureau of Vocational Rehabilitation Unit, Cleveland Psychiatric Institute, Cleveland, Ohio revealed that family type (conjugal settings, parental settings, living alone) is found to to be a valuable prognosticator of rehabilitation outcome among post-hospitalized schizophrenics. (EA)

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer.

PubMed

Zacapala-Gómez, Ana E; Navarro-Tito, Napoleón; Alarcón-Romero, Luz Del C; Ortuño-Pineda, Carlos; Illades-Aguiar, Berenice; Castañeda-Saucedo, Eduardo; Ortiz-Ortiz, Julio; Garibay-Cerdenares, Olga L; Jiménez-López, Marco A; Mendoza-Catalán, Miguel A

2018-03-27

Cervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers. Immunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot. High Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer. Ezrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.

A New Multivariate Approach for Prognostics Based on Extreme Learning Machine and Fuzzy Clustering.

PubMed

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2015-12-01

Prognostics is a core process of prognostics and health management (PHM) discipline, that estimates the remaining useful life (RUL) of a degrading machinery to optimize its service delivery potential. However, machinery operates in a dynamic environment and the acquired condition monitoring data are usually noisy and subject to a high level of uncertainty/unpredictability, which complicates prognostics. The complexity further increases, when there is absence of prior knowledge about ground truth (or failure definition). For such issues, data-driven prognostics can be a valuable solution without deep understanding of system physics. This paper contributes a new data-driven prognostics approach namely, an "enhanced multivariate degradation modeling," which enables modeling degrading states of machinery without assuming a homogeneous pattern. In brief, a predictability scheme is introduced to reduce the dimensionality of the data. Following that, the proposed prognostics model is achieved by integrating two new algorithms namely, the summation wavelet-extreme learning machine and subtractive-maximum entropy fuzzy clustering to show evolution of machine degradation by simultaneous predictions and discrete state estimation. The prognostics model is equipped with a dynamic failure threshold assignment procedure to estimate RUL in a realistic manner. To validate the proposition, a case study is performed on turbofan engines data from PHM challenge 2008 (NASA), and results are compared with recent publications.

Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer.

PubMed

Monsó, Eduard; Montuenga, Luis M; Sánchez de Cos, Julio; Villena, Cristina

2015-09-01

The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.

PubMed

Masugi, Yohei; Tanese, Keiji; Emoto, Katsura; Yamazaki, Ken; Effendi, Kathryn; Funakoshi, Takeru; Mori, Mariko; Sakamoto, Michiie

2015-12-01

Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well-conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Prognostic value of CD44 expression in penile squamous cell carcinoma: a pilot study.

PubMed

Minardi, Daniele; Lucarini, Guendalina; Filosa, Alessandra; Zizzi, Antonio; Simonetti, Oriana; Offidani, Anna Maria; d'Anzeo, Gianluca; Di Primio, Roberto; Montironi, Rodolfo; Muzzonigro, Giovanni

2012-10-01

Several studies have reported on the prognostic value of molecular markers for metastasis risk and survival in penile squamous cell carcinoma (SCC) patients. The usefulness of CD44 expression as such a marker has been studied in different tumors, but not in penile SCC. Our aim was to determine whether CD44 expression may serve as a prognostic marker for lymph node metastasis and survival in penile SCC patients. CD44 immunoistochemical expression was investigated in tissue specimens from 39 patients with penile SCC. CD44 cell positivity, staining intensity and distribution were analyzed and correlated with tumor stage, grade, lymph node status and disease-specific survival. CD44 expression was detected in epithelial cells of both intratumoral and normal tissues with different intensities and staining distributions. In normal tissues CD44 protein was mainly detected in cell membranes, whereas in the tumor compartments it was found in both the cell membranes and the cytoplasm. The intensities and percentages of CD44 expressing cells did not correlate with tumor stage and/or grade. Seventy-three percent of the patients with lymph node metastasis showed high intensities of CD44 staining, as compared to 44% of the patients without lymph node metastasis (P = 0.03). Lymph node-positive patients showed both cytoplasmic and membranous CD44 expression. High CD44 expression was found to be significantly correlated with a decreased 5 year overall survival (P = 0.01). CD44 levels and patterns of expression can be considered as markers for penile SCC aggressiveness and, in addition, may serve as predictive markers for lymph node metastasis, also in patients with clinically negative lymph nodes. CD44 expression may provide prognostic information for penile SCC patients, next to classical clinical-pathological factors.

Using prognostic models in CLL to personalize approach to clinical care: Are we there yet?

PubMed

Mina, Alain; Sandoval Sus, Jose; Sleiman, Elsa; Pinilla-Ibarz, Javier; Awan, Farrukh T; Kharfan-Dabaja, Mohamed A

2018-03-01

Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course. Accordingly, these newer models are helping develop better informed surveillance strategies and ultimately tailor treatment intensity according to presence (or lack thereof) of certain prognostic markers. This represents a step towards personalizing care of CLL patients. We anticipate that as more prognostic factors continue to be identified, the GCLLSG prognostic index and CLL-IPI models will undergo further revisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of Liver Biomarkers as Prognostic Factors for Outcomes to Yttrium-90 Radioembolization of Primary and Secondary Liver Malignancies.

PubMed

Henrie, Adam M; Wittstrom, Kristina; Delu, Adam; Deming, Paulina

2015-09-01

The objective of this study was to examine indicators of liver function and inflammation for prognostic value in predicting outcomes to yttrium-90 radioembolization (RE). In a retrospective analysis, markers of liver function and inflammation, biomarkers required to stage liver function and inflammation, and data regarding survival, tumor response, and progression after RE were recorded. Univariate regression models were used to investigate the prognostic value of liver biomarkers in predicting outcome to RE as measured by survival, tumor progression, and radiographic and biochemical tumor response. Markers from all malignancy types were analyzed together. A subgroup analysis was performed on markers from patients with metastatic colorectal cancer. A total of 31 patients received RE from 2004 to 2014. Median survival after RE for all malignancies combined was 13.6 months (95% CI: 6.7-17.6 months). Results from an exploratory analysis of patient data suggest that liver biomarkers, including albumin concentrations, international normalized ratio, bilirubin concentrations, and the model for end-stage liver disease score, possess prognostic value in predicting outcomes to RE.

Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas.

PubMed

Busch, Jonas; Ralla, Bernhard; Jung, Monika; Wotschofsky, Zofia; Trujillo-Arribas, Elena; Schwabe, Philipp; Kilic, Ergin; Fendler, Annika; Jung, Klaus

2015-06-14

Piwi-interacting RNAs (piRNAs) are small RNAs of 27-30 nucleotides mapping to transposons or clustering in repeat genomic regions. Preliminary studies suggest an important role in cancerogenesis. This study is the first one investigating their prognostic impact in clear cell renal cell cancer (ccRCC) patients. Three piRNAs (piR-30924, piR-57125, and piR-38756) selected on the basis of initial piRNA microarray analyses were determined using RT-qPCR in non-metastatic (n = 76) and metastatic (n = 30) ccRCC tissue at the time of nephrectomy in comparison to normal renal tissue (n = 77) and tissue from distant ccRCC metastases (n = 13). Primary clinical end points were recurrence-free and overall survival. piR-57125 showed lower expression in metastatic than in non-metastatic tumors, whereas the expression of piR-30924 and piR-38756 increased in metastatic tumors. The higher expression of piR-30924 and piR-38756 as well as the lower expression of piR-57125 in metastatic primary tumors were significantly associated with tumor recurrence and overall survival. Multivariate Cox regression analyses revealed both piR-30924 and piR-57125 as independent prognostic predictors. This impact was even more pronounced in non-metastatic patients. This study demonstrates that the expression levels of these piRNAs in primary non-metastatic and metastatic ccRCC tissue can serve as potential prognostic biomarkers in combination with clinicopathological factors.

Molecular markers in well-differentiated thyroid cancer.

PubMed

D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

2018-06-01

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma

PubMed Central

Shah, Monil; Mulcahy Levy, Jean M.; Griesinger, Andrea M.; Alimova, Irina; Harris, Peter S.; Birks, Diane K.; Donson, Andrew M.; Davidson, Nathan; Remke, Marc; Taylor, Michael D.; Handler, Michael H.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-01-01

Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation. PMID:27449089

Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma.

PubMed

Prince, Eric W; Balakrishnan, Ilango; Shah, Monil; Mulcahy Levy, Jean M; Griesinger, Andrea M; Alimova, Irina; Harris, Peter S; Birks, Diane K; Donson, Andrew M; Davidson, Nathan; Remke, Marc; Taylor, Michael D; Handler, Michael H; Foreman, Nicholas K; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-08-16

Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation.

Telomere length is an independent prognostic marker in MDS but not in de novo AML.

PubMed

Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

2017-07-01

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

PubMed

Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.

Clinical value of octamer-binding transcription factor 4 as a prognostic marker in patients with digestive system cancers: A systematic review and meta-analysis.

PubMed

Chen, Zhiqiang; Zhang, Long; Zhu, Qin; Wang, Xiaowei; Wu, Jindao; Wang, Xuehao

2017-03-01

The role of octamer-binding transcription factor 4 (Oct4) has been implicated in the clinical prognosis of various kinds of digestive system cancers, but the results remain controversial. The purpose of this meta-analysis is to assess the potential role of Oct4 as a prognostic marker in digestive system tumors. Relevant articles were retrieved from Pubmed, Web of Science, and Cochrane Library up to July 2016. The software Stata 12.0 was used to analyze the outcomes, including overall survival (OS), disease-free survival, recurrence-free survival, and clinicopathological characteristics. A total of 13 eligible studies with 1538 patients were included. Elevated Oct4 expression was significantly associated with poor OS (pooled hazard ratio [HR] = 2.183, 95% confidence interval [CI]: 1.824-2.612), disease-free survival (pooled HR = 1.973, 95% CI: 1.538-2.532), and recurrence-free survival (pooled HR = 2.209, 95% CI: 1.461-3.338) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection method did not alter the significant prognostic value of Oct4. Additionally, Oct4 expression was found to be an independent predictive factor for OS (HR = 2.068, 95% CI: 1.633-2.619). No significant association was found between Oct4 and clinicopathological features of digestive system malignancies. This study provided evidence of Oct4 and/or its closely related homolog protein as a predictive factor for patients with digestive system cancers. More large-scale clinical studies on the prognostic value of Oct4 are warranted. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Prevalence and Correlation of Human Papilloma Virus and its Types with Prognostic Markers in Patients with Invasive Ductal Carcinoma of the Breast in Kuwait

PubMed Central

Francis, Issam M.; Al-Ayadhy, Bushra; Al-Awadhi, Shafiqa; Kapila, Kusum; Al-Mulla, Fahd

2013-01-01

Objectives: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. Methods: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. Results: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. Conclusion: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected. PMID:24273662

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients

PubMed Central

Molloy, Timothy J.; Roepman, Paul; Naume, Bjørn; van't Veer, Laura J.

2012-01-01

The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into “good prognosis” or “poor prognosis” are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the “CTC profile” also provided prognostic information independent of the well-established and powerful ‘70-gene’ prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays. PMID:22384245

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

PubMed

Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

2018-06-01

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis.

PubMed

Kamran, Sophia C; Clark, Jeffrey W; Zheng, Hui; Borger, Darrell R; Blaszkowsky, Lawrence S; Allen, Jill N; Kwak, Eunice L; Wo, Jennifer Y; Parikh, Aparna R; Nipp, Ryan D; Murphy, Janet E; Goyal, Lipika; Zhu, Andrew X; Iafrate, A John; Corcoran, Ryan B; Ryan, David P; Hong, Theodore S

2018-05-17

Recent reports demonstrate inferior outcomes associated with primary right-sided vs left-sided colorectal tumors in patients with metastatic colorectal cancer (mCRC). We sought to describe our experience with mCRC patients on whom we have molecular data to determine whether primary tumor sidedness was an independent prognostic marker for overall survival (OS). mCRC patients with documented primary tumor sidedness who received mutational profiling between 2009 and 2014 were identified (n = 367, median follow-up 30.4 months). Mutational profiling for >150 mutations across commonly mutated cancer genes including RAS, PIK3CA, BRAF, and PTEN as well as treatment data, including receipt of a biologic agent, were collected. Univariable/multivariable models were used to analyze relationships between collected data and OS. Among 367 patients, sidedness breakdown was as follows: 234 left (64%), 133 right (36%). 56% were male, with a median age at diagnosis of 57 (range 24-89). A total of 143 patients had RAS mutations. Five-year OS was 41%, median OS was 54 months (range 1-149). Five-year OS for left- vs right-sided tumors was 46% vs 24% (P < .0001). On univariable analysis, among both RAS wildtype and mutant tumors, left-sided tumors continued to have improved OS vs right-sided tumors (HR: 0.49, 95% CI: 0.34-0.69 RAS wildtype; HR: 0.61, 95% CI: 0.40-0.95 RAS mutant). Left-sidedness was an important prognostic factor for OS among RAS wildtype patients despite treatment with or without a biologic agent (P < .05). Left-sidedness remained significant for improved OS on multivariable analysis (P < .0001). Left-sided primary tumor remained most important prognostic factor for OS, even when adjusting for mutational status and receipt of biologic agent. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The biological and prognostic significance of angiotropism in uveal melanoma.

PubMed

Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire

2017-02-27

Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of

Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

PubMed

Yasutake, Nobuko; Ohishi, Yoshihiro; Taguchi, Kenichi; Hiraki, Yuka; Oya, Masafumi; Oshiro, Yumi; Mine, Mari; Iwasaki, Takeshi; Yamamoto, Hidetaka; Kohashi, Kenichi; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

2018-04-01

The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. IMP3 expression in ULMS could be a marker of a poor prognosis. © 2017 John Wiley & Sons Ltd.

CD68/macrosialin: not just a histochemical marker.

PubMed

Chistiakov, Dimitry A; Killingsworth, Murry C; Myasoedova, Veronika A; Orekhov, Alexander N; Bobryshev, Yuri V

2017-01-01

CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk.

PubMed

Mahrooghy, Majid; Ashraf, Ahmed B; Daye, Dania; McDonald, Elizabeth S; Rosen, Mark; Mies, Carolyn; Feldman, Michael; Kontos, Despina

2015-06-01

Heterogeneity in cancer can affect response to therapy and patient prognosis. Histologic measures have classically been used to measure heterogeneity, although a reliable noninvasive measurement is needed both to establish baseline risk of recurrence and monitor response to treatment. Here, we propose using spatiotemporal wavelet kinetic features from dynamic contrast-enhanced magnetic resonance imaging to quantify intratumor heterogeneity in breast cancer. Tumor pixels are first partitioned into homogeneous subregions using pharmacokinetic measures. Heterogeneity wavelet kinetic (HetWave) features are then extracted from these partitions to obtain spatiotemporal patterns of the wavelet coefficients and the contrast agent uptake. The HetWave features are evaluated in terms of their prognostic value using a logistic regression classifier with genetic algorithm wrapper-based feature selection to classify breast cancer recurrence risk as determined by a validated gene expression assay. Receiver operating characteristic analysis and area under the curve (AUC) are computed to assess classifier performance using leave-one-out cross validation. The HetWave features outperform other commonly used features (AUC = 0.88 HetWave versus 0.70 standard features). The combination of HetWave and standard features further increases classifier performance (AUCs 0.94). The rate of the spatial frequency pattern over the pharmacokinetic partitions can provide valuable prognostic information. HetWave could be a powerful feature extraction approach for characterizing tumor heterogeneity, providing valuable prognostic information.

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

PubMed

Ishizuka, Mitsuru; Oyama, Yusuke; Abe, Akihito; Tago, Kazuma; Tanaka, Genki; Kubota, Keiichi

2014-08-01

To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niwinska, Anna, E-mail: alphaonetau@poczta.onet.pl; Murawska, Magdalena

2012-04-01

Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4more » months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of {<=}60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.« less

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Improving selection of markers in nutrition research: evaluation of the criteria proposed by the ILSI Europe Marker Validation Initiative.

PubMed

Calder, Philip C; Boobis, Alan; Braun, Deborah; Champ, Claire L; Dye, Louise; Einöther, Suzanne; Greyling, Arno; Matthys, Christophe; Putz, Peter; Wopereis, Suzan; Woodside, Jayne V; Antoine, Jean-Michel

2017-06-01

The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

The prognostic value of the systemic inflammatory score in patients with unresectable metastatic colorectal cancer.

PubMed

Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei; Ohira, Masaichi

2018-07-01

Inflammation has been widely recognized as a contributor to cancer progression and several inflammatory markers have been reported as associated with the clinical outcomes in patients with various types of cancer. Recently, a novel inflammatory marker, the systemic inflammatory score (SIS), which is based on a combination of the lymphocyte-to-monocyte ratio (LMR) and the serum albumin concentration has been reported as a useful prognostic marker. The aim of the present study was to assess the prognostic value of the SIS in patients with unresectable metastatic colorectal cancer (mCRC). The retrospective cohort study included 160 patients who underwent combination chemotherapy for unresectable mCRC between January 2008 and December 2016. The SIS was used to classify the patients into three groups based on their LMR and the serum albumin concentration. Patients with high-LMR and high serum albumin level were given a score of 0; patients with low-LMR or low serum albumin level were given a score of 1; patients with low-LMR and low serum albumin level were given a score of 2. There were significant differences in the overall survival among the three SIS groups and the SIS was an independent prognostic factor for the overall survival. Although the SIS was significantly associated with the overall survival rate even when using the original cut-off values, the SIS according to the new cut-off values had a more accurate prognostic value. The present study determined that the SIS was a useful biomarker for predicting the survival outcomes in patients with unresectable mCRC, although the optimum cut-off value of the SIS according to the patients' background needs to be examined in further studies.

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

PubMed

Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin

2017-12-01

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease?

PubMed

Martins, Marina Lobato; Guimarães, Jacqueline Cronemberger; Ribas, João Gabriel; Romanelli, Luiz Cláudio Ferreira; de Freitas Carneiro-Proietti, Anna Bárbara

2017-02-01

HTLV-1 proviral load (pvl) is an important risk marker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its value as prognostic marker is not well defined. Long-term prospective cohort studies are necessary to clarify this question. Here, we analyzed HTLV-1 pvl in the peripheral blood of 82 asymptomatic carriers (AC; 351 samples), 12 HAM/TSP patients (HAM; 46 samples), and six incident cases of HAM/TSP (iHAM), with serial samples collected before (n = 10) and after (n = 20) the disease onset. The mean interval of follow-up was 10 years in the AC group and 8 years in HAM and iHAM groups. pvl was not significantly different between the first and last measurements in the three groups, but there was a trend to decrease over time. Coefficient of variation of pvl was significantly lower in the AC group than in HAM (p = 0.015) and iHAM (p = 0.022) patients. AC and HAM individuals showed a significant and strong positive correlation between the first and last measurements of pvl, but not iHAM subjects. All individuals who developed HAM/TSP during the follow-up had high pvl level (>1 %) before the onset of disease, but a typical increase in pvl was not observed in that period. The data suggest that there is a trend to reach an equilibrium plateau of pvl over time, characteristic of each individual. A significant rate of AC keeps high pvl levels for a long time without developing clinical symptoms associated to HTLV-1 infection. Thus, serial quantification of pvl in the peripheral blood does not seem to be a good prognostic marker for HAM/TSP.

Usefulness of quantitative polymerase chain reaction in amniotic fluid as early prognostic marker of fetal infection with Toxoplasma gondii.

PubMed

Romand, Stéphane; Chosson, Muriel; Franck, Jacqueline; Wallon, Martine; Kieffer, François; Kaiser, Karine; Dumon, Henri; Peyron, François; Thulliez, Philippe; Picot, Stéphane

2004-03-01

Our purpose was to evaluate Toxoplasma gondii concentration in amniotic fluid (AF) samples as a prognostic marker of congenital toxoplasmosis. A retrospective study was carried out in 88 consecutive AF samples from 86 pregnant women, which were found positive by prospective polymerase chain reaction (PCR) testing. Parasite AF concentrations were estimated by real-time quantitative PCR and analyzed in relation to the clinical outcome of infected fetuses during pregnancy and at birth, taking into account the gestational age at maternal infection. A significant negative linear regression was observed between gestational age at maternal infection and T gondii DNA loads in AF. After adjusting for time at maternal seroconversion by multivariate analysis, higher parasite concentrations were significantly associated with a severe outcome of congenital infection (odds ratio [OR]=15.38/log (parasites/mL AF) [95% CI=2.45-97.7]). PCR quantification of T gondii in AF can be highly contributive for early prognosis of congenital toxoplasmosis. Maternal infections acquired before 20 weeks with a parasite load greater than 100/mL of AF have the highest risk of severe fetal outcome.

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

PubMed Central

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

Serum Uric Acid Level as a Prognostic Marker in Patients With Acute Respiratory Distress Syndrome.

PubMed

Lee, Hyun Woo; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Sang-Min

2017-01-01

Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS. A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed. Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level <3.0 mg/dL were classified into the low uric acid group, and those with a level ≥3 mg/dL were classified into the normal to high uric acid group. We selected 40 patients in each group using propensity score matching. A higher percentage of patients in the low uric acid group experienced clinical improvement in ARDS. More patients died from sepsis in the normal to high uric acid group. Kaplan-Meier analysis showed that a low serum uric acid level was significantly associated with better survival rate. In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.

Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models.

PubMed

Vermaat, J S; van der Tweel, I; Mehra, N; Sleijfer, S; Haanen, J B; Roodhart, J M; Engwegen, J Y; Korse, C M; Langenberg, M H; Kruit, W; Groenewegen, G; Giles, R H; Schellens, J H; Beijnen, J H; Voest, E E

2010-07-01

In metastatic renal cell cancer (mRCC), the Memorial Sloan-Kettering Cancer Center (MSKCC) risk model is widely used for clinical trial design and patient management. To improve prognostication, we applied proteomics to identify novel serological proteins associated with overall survival (OS). Sera from 114 mRCC patients were screened by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). Identified proteins were related to OS. Three proteins were subsequently validated with enzyme-linked immunosorbent assays and immunoturbidimetry. Prognostic models were statistically bootstrapped to correct for overestimation. SELDI-TOF MS detected 10 proteins associated with OS. Of these, apolipoprotein A2 (ApoA2), serum amyloid alpha (SAA) and transthyretin were validated for their association with OS (P = 5.5 x 10(-9), P = 1.1 x 10(-7) and P = 0.0004, respectively). Combining ApoA2 and SAA yielded a prognostic two-protein signature [Akaike's Information Criteria (AIC) = 732, P = 5.2 x 10(-7)]. Including previously identified prognostic factors, multivariable Cox regression analysis revealed ApoA2, SAA, lactate dehydrogenase, performance status and number of metastasis sites as independent factors for survival. Using these five factors, categorization of patients into three risk groups generated a novel protein-based model predicting patient prognosis (AIC = 713, P = 4.3 x 10(-11)) more robustly than the MSKCC model (AIC = 729, P = 1.3 x 10(-7)). Applying this protein-based model instead of the MSKCC model would have changed the risk group in 38% of the patients. Proteomics and subsequent validation yielded two novel prognostic markers and survival models which improved prediction of OS in mRCC patients over commonly used risk models. Implementation of these models has the potential to improve current risk stratification, although prospective validation will still be necessary.

Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.

PubMed

Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

2012-04-01

Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future.

Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

PubMed

Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

2017-03-01

Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Small biparietal diameter and head circumference are part of the phenotype instead of independent prognostic markers in fetuses with spinal dysraphism.

PubMed

Cuppen, Inge; de Bruijn, Dagmar; Geerdink, Niels; Rotteveel, Jan J; Willemsen, Michèl A A P; van Vugt, John M G; Pasman, Jaco W; Roeleveld, Nel

2015-01-01

The aim of this retrospective study was to assess the fetal biparietal diameter (BPD) and head circumference (HC) in the second trimester of pregnancy in fetuses with open spinal dysraphism. BPD and HC were measured at 16-26 weeks in 74 fetuses with open spinal dysraphism and compared with reference values. BPD was smaller in fetuses with open spinal dysraphism. Of all cases with open spinal dysraphism, 62.2% had a BPD <3rd percentile and 79.7% had a BPD <10th percentile. Of all patients, 54.1% had an HC <3rd percentile and 74.3% had an HC <10th percentile. Almost all fetuses with open neural tube defects have a smaller BPD and HC at 16-26 weeks compared with reference values, which implicates that this is part of the phenotype of children with open spinal dysraphism instead of an independent prognostic marker for a poor cognitive outcome. © 2014 S. Karger AG, Basel.

C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: results from the OPTIMAAL study.

PubMed

Voors, Adriaan A; von Haehling, Stephan; Anker, Stefan D; Hillege, Hans L; Struck, Joachim; Hartmann, Oliver; Bergmann, Andreas; Squire, Iain; van Veldhuisen, Dirk J; Dickstein, Kenneth

2009-05-01

The aim of the present study was to compare the prognostic value of a novel and promising marker, copeptin, with B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), on death or a composite cardiovascular endpoint in patients who developed heart failure after an acute myocardial infarction (AMI). From a subset of 224 patients of the OPTIMAAL study, blood samples were drawn at a mean of 3 days after AMI when all patients had signs and/or symptoms of heart failure or a left ventricular ejection fraction <0.35. Endpoints of interest were mortality (primary endpoint of OPTIMAAL) and a composite cardiovascular endpoint, including death, MI, stroke, and/or resuscitated cardiac arrest. Mean age was 67 +/- 10 years, and mean follow-up was 33 +/- 7 months. Using univariable Cox proportional hazards survival analysis, higher levels of copeptin, BNP, and NT-proBNP were all significantly related to both mortality and the composite cardiovascular endpoint (all P < 0.01). In a multivariable Cox proportional hazards model, including all three biomarkers and other relevant covariates, a doubling of copeptin was related to a 1.83 (1.26-2.64) times increased risk of mortality (P < 0.0001) and a 1.35 (1.05-1.72) times increased risk of the composite cardiovascular endpoint (P = 0.018). Receiver operating characteristic curves indicated that copeptin [area under curve (AUC) 0.81] was a stronger predictor of mortality compared with both BNP (AUC 0.66; P = 0.0063 vs. copeptin) and NT-proBNP (AUC 0.67; P = 0.0016 vs. copeptin). Finally, changes of copeptin levels after 1 month significantly added prognostic information to the baseline value. Copeptin is a strong and novel marker for mortality and morbidity in patients with heart failure after AMI. In this population, the predictive value of copeptin was even stronger than BNP and NT-proBNP.

Prognostic relevance of epithelial-mesenchymal transition and proliferation in surgically treated primary parotid gland cancer.

PubMed

Busch, Alina; Bauer, Larissa; Wardelmann, Eva; Rudack, Claudia; Grünewald, Inga; Stenner, Markus

2017-05-01

Cancer of the major salivary glands comprises a morphologically diverse group of rare tumours of largely unknown cause. Epithelial-mesenchymal transition (EMT) has been shown to play a significant prognostic role in various human cancers. The aim was to assess the expression of EMT markers in different histological subtypes of parotid gland cancer (PGC) and analyse their prognostic value. We examined 94 PGC samples (13 histological subtypes) for the expression of MIB-1, epithelial cadherin (E-cadherin), β-catenin, vimentin and cytokeratin 8/18 (CK8/18) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. We detected all analysed EMT and proliferation markers in specifically different constellations within the examined histological subtypes of PGC. We found high epithelial marker expressions (CK8/18, E-cadherin, membranous β-catenin) only in a distinct variety of carcinomas. A high proliferation rate (high MIB-1 expression) as well as a combination of high CK8/18 and low vimentin expression was associated with a significantly worse survival. Our findings indicate that activation of the EMT pathway is a relevant explanation for tumour progression in individual histological subtypes of malignant parotid gland lesions, but by far not in all. Evidence of EMT activation in PGC cannot be seen as an isolated prognostic factor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prognostic marker for liver disease due to alpha1-antitrypsin deficiency.

PubMed

Pferdmenges, D C; Baumann, U; Müller-Heine, A; Framke, T; Pfister, E-D

2013-09-01

Only some Alpha1-antitrypsin deficiency (A1ATD) PiZZ patients develop liver cirrhosis and portal hypertension. Aim of the study was to investigate the course of liver disease associated with PiZZ A1ATD and to determine prognostic factors. We retrospectively reviewed the clinical and laboratory data of all PiZZ children up to 18 years of age admitted to our centre since 1978. 53 patients (age at first visit 2 days to 12 years) met our criteria. The children were divided into 2 groups: group 1 'bad prognosis', meaning the patients which were on the waiting list for liver transplantation (LTx), had a liver transplantation or had died, and group 2 'good prognosis', containing the patients they were living with their own liver. We analysed family history including smoking, gestational age, maternal age at delivery, date of birth, sex, neonatal history, breast-feeding, symptoms at presentation, clinical and laboratory data and date of LTx and/or death. Various anamnesis parameters such as manifestation of neonatal cholestasis showed no prognostic significance. In contrast the laboratory parameters thrombocytes (p=0.008), bilirubin (p<0.001), prothrombin time (p<0.001), choline-sterase (p<0.001), gamma-GT (p=0.001) and GOT (p=0.002) showed a correlation with a liver transplantation and/or death. Prognosis is difficult to determine at an early stage of this disease, but various laboratory parameters can help to predict an outcome. Therefore a regular follow-up is necessary for the children. © Georg Thieme Verlag KG Stuttgart · New York.

Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer.

PubMed

Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

2012-02-28

The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer.

Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer

PubMed Central

Sun, Xu-Ren; Sun, Zhe; Zhu, Zhi; Guan, Hai-Xia; Li, Chen-Yan; Zhang, Jun-Yan; Zhang, Yi-Ning; Zhou, Huan; Zhang, Hui-Jing; Xu, Hui-Mian; Sun, Ming-Jun

2015-01-01

AIM: To investigate the expression and prognostic role of pyruvate dehydrogenase (PDH) in gastric cancer (GC). METHODS: This study included 265 patients (194 male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007. All patients were followed up for more than 5 years. Patient-derived paraffin embedded GC specimens were collected for tissue microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was evaluated independently by two researchers. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by two-tailed χ2 tests or a two-tailed t-test. The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis. RESULTS: Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001), lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P = 0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P = 0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001) in GC. PDH expression in cancer tissue was significantly associated with higher OS (P < 0.001). The multivariate analysis adjusted for age, Lauren classification, TNM stage, lymph node metastasis, histological type, tumor size, depth of invasion and lymphatic invasion

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Study of the diagnosis and treatment of cancer located in the head and neck and correlation with expression of prognostic markers.

PubMed

Bădulescu, Fl; Bădulescu, Adriana; Crişan, Anda; Popescu, Florina Carmen

2013-01-01

A prospective study made by authors was initiated in 2000 in order to analyze differences in terms of response rate, overall survival and progression free survival for patients with advanced head and neck carcinoma treated with radiotherapy vs. radiochemotherapy, respectively and to analyze the role of modern molecular biomarkers in the prognosis of these patients (p53, EGFR and Ki67). It was detected one significant difference appeared between the two groups for response rate (p<0.0001) and median overall survival [18.8 months in Group A and 17.2 months in Group B, with a hazard ratio for survival of 0.88 (95% CI, 0.75-1.12, p<0.0001]. Progression free survival was not significant different between these two groups [6.9 months for Group A and 7.2 months for Group B, p=0.3179]. Multivariate analysis by sex, age, TNM stage, site of disease, revealed TNM stage and site of disease as clinical phenotypes with predictive value. Also, the molecular biomarkers p53, EGFR and Ki67 have a prognostic significance in head and neck cancer in addition to the established clinical prognostic factors such as the stage, site of the tumor and the type of treatment. Because of material reasons, we decided to carry out the immunohistochemical marking in the group of patients who were radiochemotherapy-treated and the results of multivariate analysis reached statistical significance threshold in terms of response rate to treatment, overall survival and disease-free interval. Furthermore, immunohistochemical examination was not performed for patients with rhinopharyngeal carcinoma with marked radiochemosensibility and reduced tumor aggressiveness reflected in significantly better therapeutic outcomes by treatment response rate, overall survival and disease free interval. In the present study of the 93 cases that underwent immunohistochemical staining for EGFR, the majority (66 cases) showed a positive reaction for this marker, in 36 cases are highly immunohistochemical staining, and in

Field‐readable alphanumeric flags are valuable markers for shorebirds: use of double‐marking to identify cases of misidentification

USGS Publications Warehouse

Roche, Erin A.; Dovichin, Colin M.; Arnold, Todd W.

2014-01-01

Implicit assumptions for most mark-recapture studies are that individuals do not lose their markers and all observed markers are correctly recorded. If these assumptions are violated, e.g., due to loss or extreme wear of markers, estimates of population size and vital rates will be biased. Double-marking experiments have been widely used to estimate rates of marker loss and adjust for associated bias, and we extended this approach to estimate rates of recording errors. We double-marked 309 Piping Plovers (Charadrius melodus) with unique combinations of color bands and alphanumeric flags and used multi-state mark recapture models to estimate the frequency with which plovers were misidentified. Observers were twice as likely to read and report an invalid color-band combination (2.4% of the time) as an invalid alphanumeric code (1.0%). Observers failed to read matching band combinations or alphanumeric flag codes 4.5% of the time. Unlike previous band resighting studies, use of two resightable markers allowed us to identify when resighting errors resulted in reports of combinations or codes that were valid, but still incorrect; our results suggest this may be a largely unappreciated problem in mark-resight studies. Field-readable alphanumeric flags offer a promising auxiliary marker for identifying and potentially adjusting for false-positive resighting errors that may otherwise bias demographic estimates.

Comparison of Prognostic and Diagnostic Approaches to Modeling Evapotranspiration in the Nile River Basin

NASA Astrophysics Data System (ADS)

Yilmaz, M.; Anderson, M. C.; Zaitchik, B. F.; Crow, W. T.; Hain, C.; Ozdogan, M.; Chun, J. A.

2012-12-01

Actual evapotranspiration (ET) can be estimated using both prognostic and diagnostic modeling approaches, providing independent yet complementary information for hydrologic applications. Both approaches have advantages and disadvantages. When provided with temporally continuous atmospheric forcing data, prognostic models offer continuous sub-daily ET information together with the full set of water and energy balance fluxes and states (i.e. soil moisture, runoff, sensible and latent heat). On the other hand, the diagnostic modeling approach provides ET estimates over regions where reliable information about available soil water is not known (e.g., due to irrigation practices or shallow ground water levels not included in the prognostic model structure, unknown soil texture or plant rooting depth, etc). Prognostic model-based ET estimates are of great interest whenever consistent and complete water budget information is required or when there is a need to project ET for climate or land use change scenarios. Diagnostic models establish a stronger link to remote sensing observations, can be applied in regions with limited or questionable atmospheric forcing data, and provide valuable observation-derived information about the current land-surface state. Analysis of independently obtained ET estimates is particularly important in data poor regions. Such comparisons can help to reduce the uncertainty in the modeled ET estimates and to exclude outliers based on physical considerations. The Nile river basin is home to tens of millions of people whose daily life depends on water extracted from the river Nile. Yet the complete basin scale water balance of the Nile has been studied only a few times, and the temporal and the spatial distribution of hydrological fluxes (particularly ET) are still a subject of active research. This is due in part to a scarcity of ground-based station data for validation. In such regions, comparison between prognostic and diagnostic model output

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

PubMed Central

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sando; Roggero, Enrico; Stanta, Giorgio

2016-01-01

Abstract Background Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. Patients and methods NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. Results NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. Conclusions A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID:27679548

RON is not a prognostic marker for resectable pancreatic cancer.

PubMed

Tactacan, Carole M; Chang, David K; Cowley, Mark J; Humphrey, Emily S; Wu, Jianmin; Gill, Anthony J; Chou, Angela; Nones, Katia; Grimmond, Sean M; Sutherland, Robert L; Biankin, Andrew V; Daly, Roger J

2012-09-07

The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.

Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients.

PubMed

Grimminger, Peter P; Maus, Martin K H; Bergenthal, Juliane; Wandhöfer, Christoph; Fetzner, Ullrich K; Herbold, Till; Bollschweiler, Elfriede; Hölscher, Arnulf H; Brabender, Jan

2015-03-01

The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal cancer. A total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0) were enrolled in this prospective study. All patients received neoadjuvant chemoradiation followed by a transthoracic resection (curative transthoracic en bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of therapy. The analysis was performed using quantitative real-time-polymerase chain reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant therapy was defined as follows: major response (MaR)=less than 10% vital tumor tissue, minor response (MiR)=more than 10% vital tumor tissue. Nineteen out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes, the RNA expression of TS was significantly associated with prognosis of patients. Patients with TS expression above 0.78 had a median survival of 1.1 years (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS expression lower than 0.78 (p=0.031, log rank test). There was no association between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA expression of TS in the serum. The RNA expression of TS in the blood is a potential prognostic marker in patients with neoadjuvant-treated esophageal cancer. The significance of these molecular alterations as non-invasive prognostic marker for esophageal cancer should be evaluated in prospective studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis.

PubMed

Hussain, Azhar R; Siraj, Abdul Khalid; Ahmed, Maqbool; Bu, Rong; Pratheeshkumar, Poyil; Alrashed, Alanood M; Qadri, Zeeshan; Ajarim, Dahish; Al-Dayel, Fouad; Beg, Shaham; Al-Kuraya, Khawla S

2017-09-11

Breast cancer is the most common cancer in females and is ranked second in cancer-related deaths all over the world in women. Despite improvement in diagnosis, the survival rate of this disease has still not improved. X-linked Inhibitor of Apoptosis (XIAP) has been shown to be over-expressed in various cancers leading to poor overall survival. However, the role of XIAP in breast cancer from Middle Eastern region has not been fully explored. We examined the expression of XIAP in more than 1000 Middle Eastern breast cancer cases by immunohistochemistry. Apoptosis was measured by flow cytometry. Protein expression was determined by western blotting. Finally, in vivo studies were performed on nude mice following xenografting and treatment with inhibitors. XIAP was found to be over-expressed in 29.5% of cases and directly associated with clinical parameters such as tumor size, extra nodal extension, triple negative breast cancer and poorly differentiated breast cancer subtype. In addition, XIAP over-expression was also significantly associated with PI3-kinase pathway protein; p-AKT, proliferative marker; Ki-67 and anti-apoptotic marker; PARP. XIAP over-expression in our cohort of breast cancer was an independent poor prognostic marker in multivariate analysis. Next, we investigated inhibition of XIAP using a specific inhibitor; embelin and found that embelin treatment led to inhibition of cell viability and induction of apoptosis in breast cancer cells. Finally, breast cancer cells treated with combination of embelin and PI3-kinase inhibitor; LY294002 synergistically induced apoptosis and caused tumor growth regression in vivo. These data suggest that XIAP may be playing an important role in the pathogenesis of breast cancer and can be therapeutically targeted either alone or in combination with PI3-kinase inhibition to induce efficient apoptosis in breast cancer cells.

Serum uric acid as prognostic marker of coronary heart disease (CHD).

PubMed

Purnima, Samudrala; El-Aal, Bahiga Galal Abd

A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardio vascular and renal diseases especially in patients with diabetes mellitus, hypertension. Hyperuricemia is a risk factor of coronary heart disease. Several studies showed positive association between hyperuricemia and CHD risk factors. To analyze the serum uric acid levels in patients with diabetes and hypertension, which helps in understanding its role as prognostic marker of coronary heart disease. The study was conducted in population of Wadi-Al Dawasir (K.S.A.) aged 20-80 years through random sampling from October 2012 to June 2013. It included 250 samples and the cases were categorized into diabetic and hypertensive. In the cases, purely hypertensive were 52, diabetic were 57 and mixed group included both diabetic and hypertensive patients 65. Fasting blood was collected to analyze lipid profile which included (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein) and serum uric acid in association with age and heredity was also studied. Patient demographics were recorded. The study revealed significant association of serum uric acid (p<0.014*) and total cholesterol (p<0.007**) triglycerides (p<0.009**) low density lipoprotein (p<0.044*) in hypertensive group. Serum uric acid levels in the mixed group patients with diabetes and hypertension reported serum uric acid (p<0.0037), total cholesterol (p<0.089+) proved to have increased risk of coronary heart disease. When compared to controls (non-diabetic p<0.529) and (non-hypertensive p<0.021*) with respect to serum uric acid levels show the magnitude of risk to coronary heart disease. With progressing age the association of lipid profile and serum uric acid reported (p<0.001**) in diabetics. Significant correlations were found between serum uric acid and risk factors for CHD. This is first study of its kind in this region

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis.

PubMed

Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor

2016-03-28

To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

PubMed

Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

2016-01-01

Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status.

PubMed

Schmitz, Klaus Juergen; Ademi, Ceflije; Bertram, Stefanie; Schmid, Kurt Werner; Baba, Hideo Andreas

2016-07-22

Autophagy is a cellular pathway that regulates transportation of cytoplasmic macromolecules and organelles to lysosomes for degradation. Autophagy is involved in both tumorigenesis and tumour suppression. Here we investigated the potential prognostic value of the autophagy-related proteins Beclin-1, p62, LC3 and uncoordinated (UNC) 51-like kinase 1 (ULK1) in a cohort of colorectal cancer (CRC) specimens. In this study, we analysed the immunoexpression of the autophagy-related proteins p62, LC3, Beclin-1 and ULK1 in 127 CRC patients with known KRAS mutational status and detailed clinical follow-up. Survival analysis of p62 staining showed a significant correlation of cytoplasmic (not nuclear) p62 expression with a favourable tumour-specific overall survival (OS). The prognostic power of cytoplasmic p62 was found in the KRAS-mutated subgroup but was lost in the KRAS wildtype subgroup. Survival analysis of Beclin-1 staining did not show an association with OS in the complete cohort. LC3 overexpression demonstrated a slight, though not significant, association with decreased OS. Upon stratifying cases by KRAS mutational status, nuclear (not cytoplasmic) Beclin-1 staining was associated with a significantly decreased OS in the KRAS-mutated subgroup but not in the KRAS wildtype CRCs. In addition, LC3 overexpression was significantly associated with decreased OS in the KRAS-mutated CRC subgroup. ULK1 expression was not correlated to survival. Immunohistochemical analyses of LC3, p62 and Beclin-1 may constitute promising novel prognostic markers in CRC, especially in KRAS-mutated CRCs. This strategy might help in identifying high-risk patients who would benefit from autophagy-related anticancer drugs.

Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer

PubMed Central

Han, Wonshik; Han, Mi-Ryung; Kang, Jason Jongho; Bae, Ji-Yeon; Lee, Ji Hyun; Bae, Young Ju; Lee, Jeong Eon; Shin, Hyuk-Jae; Hwang, Ki-Tae; Hwang, Sung-Eun; Kim, Sung-Won; Noh, Dong-Young

2006-01-01

Background A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. Methods We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). Results Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). Conclusion Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples. PMID:16608533

Doubt and belief in physicians' ability to prognosticate during critical illness: The perspective of surrogate decision makers

PubMed Central

Zier, Lucas S.; Burack, Jeffrey H.; Micco, Guy; Chipman, Anne K.; Frank, James A.; Luce, John M.; White, Douglas B.

2009-01-01

Objectives: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Design, Setting, and Patients: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Measurements and Main Results: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic

Serum tumor markers in breast cancer: are they of clinical value?

PubMed

Duffy, Michael J

2006-03-01

Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.

The prognostic value of histidine-rich glycoprotein RNA in breast tissue using unmodified gold nanoparticles assay.

PubMed

Eissa, Sanaa; Azzazy, Hassan M E; Matboli, Marwa; Shawky, Sherif M; Said, Hebatallah; Anous, Fatin A

2014-09-01

The aim of is this study is to explore the role of tissue histidine-rich glycoprotein (HRG) RNA as a promising clinically useful biomarker for breast cancer patients prognosis using nanogold assay. Expression of the HRG RNA was assessed by gold nanoparticles and conventional RT-PCR after purification by magnetic nanoparticles in breast tissue samples. The study included 120 patients, 60 of which were histologically proven breast carcinoma cases, 30 had benign breast lesions and 30 were healthy individuals who had undergone reductive plastic surgery. ER, PR and HER2 status were also investigated. The prognostic significance of tissue HRG RNA expression in breast cancer was explored. The magnetic nanoparticles coated with specific thiol modified oligonucleotide probe were used successfully in purification of HRG RNA from breast tissue total RNAs with satisfactory yield. The developed HRG AuNPs assay had a sensitivity and a specificity of 90 %, and a detection limit of 1.5 nmol/l. The concordance rate between the HRG AuNPs assay with RT-PCR after RNA purification using magnetic nanoparticles was 93.3 %. The median follow-up period was 60 months. Among traditional prognostic biomarkers, HRG was a significant independent prognostic marker in relapse-free survival (RFS). HRG RNA is an independent prognostic marker for breast cancer and can be detected using gold NPs assay, which is rapid, sensitive, specific, inexpensive to extend the value for breast cancer prognosis.

Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis.

PubMed

Li, Xiaoping; Zhao, Haojie; Gu, Jianchun; Zheng, Leizhen

2015-01-01

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.

Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease.

PubMed

von Haehling, Stephan; Papassotiriou, Jana; Hartmann, Oliver; Doehner, Wolfram; Stellos, Konstantinos; Geisler, Tobias; Wurster, Thomas; Schuster, Andreas; Botnar, Rene M; Gawaz, Meinrad; Bigalke, Boris

2012-11-01

In the present study, we investigated the prognostic value of MR-proANP (mid-regional pro-atrial natriuretic peptide). We consecutively evaluated a catheterization laboratory cohort of 2700 patients with symptomatic CAD (coronary artery disease) [74.1% male; ACS (acute coronary syndrome), n=1316; SAP (stable angina pectoris), n=1384] presenting to the Cardiology Department of a large primary care hospital, all of whom underwent coronary angiography. Serum MR-proANP and other laboratory markers were sampled at the time of presentation or in the catheterization laboratory. Clinical outcome was assessed by hospital chart analysis and telephone interviews. The primary end point was all-cause death at 3 months after enrolment. Follow-up data were complete in 2621 patients (97.1%). Using ROC (receiver operating characteristic) curves, the AUC (area under the curve) of 0.73 [95% CI (confidence interval), 0.67-0.79] for MR-proANP was significantly higher compared with 0.58 (95% CI, 0.55-0.62) for Tn-I (troponin-I; DeLong test, P=0.0024). According to ROC analysis, the optimal cut-off value of MR-proANP was at 236 pmol/l for all-cause death, which helped to find a significantly increased rate of all-cause death (n=76) at 3 months in patients with elevated baseline concentrations (≥236 pmol/l) compared with patients with a lower concentration level in Kaplan-Meier survival analysis (log rank, P<0.001). The predictive performance of MR-proANP was independent of other clinical variables or cardiovascular risk factors, and superior to that of Tn-I or other cardiac biomarkers (all: P<0.0001). MR-proANP may help in the prediction of all-cause death in patients with symptomatic CAD. Further studies should verify its prognostic value and confirm the appropriate cut-off value.

Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer

PubMed Central

Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

2012-01-01

Background: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Methods: Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Results: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Conclusion: Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer. PMID:22294182

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

PubMed Central

2012-01-01

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department. PMID:22264220

Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

PubMed Central

Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Chaliasos, Nikolaos

2017-01-01

Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (<3 months), persistent (3–12), and chronic (>12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years (p = 0.015) and have gradual initiation of the disease (p = 0.001), platelets > 10 × 109/L (p = 0.01), and impaired immunological markers (p < 0.003) compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group (p = 0.013). None of the children exhibited severe spontaneous bleeding. Conclusion. Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice. PMID:29362564

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

PubMed Central

McCormick Matthews, L H; Noble, F; Tod, J; Jaynes, E; Harris, S; Primrose, J N; Ottensmeier, C; Thomas, G J; Underwood, T J

2015-01-01

Background: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers. Methods: Relevant articles were identified via Ovid medline 1946–2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis. Results: A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15–3.79), CD3 (HR=0.51, 95% CI=0.32–0.70), CD8 (HR=0.55, CI=0.31–0.80) and EGFR (HR=1.65, 95% CI=1.14–2.16). Discussion: Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers. PMID:26110972

Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma.

PubMed

Suchorska, Bogdana; Giese, Armin; Biczok, Annamaria; Unterrainer, Marcus; Weller, Michael; Drexler, Mark; Bartenstein, Peter; Schüller, Ulrich; Tonn, Jörg-Christian; Albert, Nathalie L

2018-01-22

Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification. Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTPmin with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTPmin >17.5 minutes (P < 0.001 for PFS and OS). Lower TBRmax values or the absence of 18F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTPmin was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group. 18F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

C-reactive protein as an adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): confirmatory results

PubMed Central

Prins, Renee C.; Rademacher, Brooks L.; Mongoue-Tchokote, Solange; Alumkal, Joshi J.; Graff, Julie N.; Eilers, Kristine M.; Beer, Tomasz M.

2010-01-01

We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with castration-resistant prostate cancer (CRPC). To confirm this finding in an independent data set, we used 119 CRPC patients enrolled in 6 phase II clinical trials and examined the relationship of CRP, alkaline phosphatase, hemoglobin, age, ECOG PS, and prostate specific antigen (PSA) with survival. Median follow-up was 19.7 months (0.9–98.5 months) and 89% have died. After analyzing the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L. In a Cox multivariate model, log2(CRP) (HR 1.106 p=0.013) as well as hemoglobin and alkaline phosphatase were independently associated with survival, confirming that higher CRP is associated with shorter survival in CRPC. Since CRP is a marker of inflammation, this finding suggests that inflammation may play an important role in the natural history of advanced prostate cancer. CRP is a readily measurable biomarker that has the potential to improve prognostic models and should be validated in a prospective clinical trial. PMID:20207556

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis.

PubMed

Aust, D E; Muders, M; Köhler, A; Schmidt, M; Diebold, J; Müller, C; Löhrs, U; Waldman, F M; Baretton, G B

2004-08-01

Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the prognostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when > or =40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic marker for overall survival (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.

Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran

PubMed Central

Nazemalhosseini Mojarad, Ehsan; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Almasi, Shohre; Chaleshi, Vahid; Kishani Farahani, Roya; Tarban, Peyman; Molaei, Mahsa; Zali, Mohammad Reza; J.K. Kuppen, Peter

2015-01-01

Background: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. Objectives: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. Patients and Methods: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. Results: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome

PubMed Central

Janik, Stefan; Raunegger, Thomas; Hacker, Philipp; Ghanim, Bahil; Einwallner, Elisa; Müllauer, Leonhard; Schiefer, Ana-Iris; Moser, Julia; Klepetko, Walter; Ankersmit, Hendrik Jan; Moser, Bernhard

2018-01-01

Background Peripheral blood-derived inflammation-based markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Fibrinogen have been identified as prognostic markers in various solid malignancies. Here we aimed to investigate the prognostic and diagnostic impact of NLR, PLR, and Fibrinogen in patients with thymic epithelial tumors (TETs). Results Pretreatment Fibrinogen serum concentrations, NLRs and PLRs were highest in patients with TCs and advanced tumor stages. High pretreatment Fibrinogen serum concentration (≥452.5 mg/dL) was significantly associated with worse cause specific survival (CSS; p = 0.001) and freedom from recurrence (FFR; p = 0.043), high NLR (≥4.0) with worse FFR (p = 0.008), and high PLR (≥136.5) with worse CSS (p = 0.032). Longitudinal analysis revealed that compared to patients without tumor recurrence, patients with tumor recurrence had significantly higher NLR (11.8 ± 4.0 vs. 4.70 ± 0.5; p = 0.001) and PLR (410.8 ± 149.1 vs. 228.3 ± 23.7; p = 0.031). Conclusion Overall, Fibrinogen serum concentrations, NLRs, and PLRs were associated with higher tumor stage, more aggressive tumor behavior, recurrence, and worse outcome. Prospective multicenter studies of the diagnostic and prognostic potential of Fibrinogen, NLR, and PLR are warranted. Methods This retrospective analysis included 122 patients with TETs who underwent surgical resection between 1999-2015. Fibrinogen serum concentrations, NLRs, and PLRs were measured in patients preoperatively, postoperatively, and later during follow-up. These markers were analyzed for association with several clinical variables, including tumor stage, tumor subtype, FFR, and CSS and to evaluate their prognostic and diagnostic impact for detecting tumor recurrence. PMID:29774108

Molecular markers: Implications for cytopathology and specimen collection.

PubMed

VanderLaan, Paul A

2015-08-01

Cytologic specimens obtained through minimally invasive biopsy techniques are increasingly being used as principle diagnostic specimens for tumors arising in multiple sites. The number and scope of ancillary tests performed on these specimens have grown substantially over the past decade, including many molecular markers that not only can aid in formulating accurate and specific diagnoses but also can provide prognostic or therapeutic information to help direct clinical decisions. Thus, the cytopathologist needs to ensure that adequate material is collected and appropriately processed for the study of relevant molecular markers, many of which are specific to tumor site. This brief review covers considerations for effective cytologic specimen collection and processing to ensure diagnostic and testing success. In addition, a general overview is provided of molecular markers pertinent to tumors from a variety of sites. The recognition of these established and emerging molecular markers by cytopathologists is an important step toward realizing the promise of personalized medicine. © 2015 American Cancer Society.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

PubMed

Brownrigg, J R W; Hinchliffe, R J; Apelqvist, J; Boyko, E J; Fitridge, R; Mills, J L; Reekers, J; Shearman, C P; Zierler, R E; Schaper, N C

2016-01-01

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation. Copyright © 2015 John Wiley & Sons, Ltd.

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma

PubMed Central

2013-01-01

Background Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. Methods One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. Results Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. Conclusions Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status. PMID:23374755

Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

PubMed

Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

2013-01-01

To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

GPU Accelerated Prognostics

NASA Technical Reports Server (NTRS)

Gorospe, George E., Jr.; Daigle, Matthew J.; Sankararaman, Shankar; Kulkarni, Chetan S.; Ng, Eley

2017-01-01

Prognostic methods enable operators and maintainers to predict the future performance for critical systems. However, these methods can be computationally expensive and may need to be performed each time new information about the system becomes available. In light of these computational requirements, we have investigated the application of graphics processing units (GPUs) as a computational platform for real-time prognostics. Recent advances in GPU technology have reduced cost and increased the computational capability of these highly parallel processing units, making them more attractive for the deployment of prognostic software. We present a survey of model-based prognostic algorithms with considerations for leveraging the parallel architecture of the GPU and a case study of GPU-accelerated battery prognostics with computational performance results.

Long Noncoding RNA HOTAIR as an Independent Prognostic Marker in Cancer: A Meta-Analysis

PubMed Central

Yang, Guang; Gu, Fang; Li, Minrui; Zhong, Bihui; Hu, Jifan; Hoffman, Andrew; Chen, Minhu

2014-01-01

Background HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy. Methods A quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results Nineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68–2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62–3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25–6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81–16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88–10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38–6.04) without obvious heterogeneity. Conclusions HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

PubMed

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis

PubMed Central

Shao, Yingjie; Xu, Bin; Chen, Lujun; Zhou, Qi; Hu, Wenwei; Zhang, Dachuan; Wu, Changping; Tao, Min; Zhu, Yibei; Jiang, Jingting

2017-01-01

Background In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. Materials and methods We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity. Results A total of 31 observational studies including 4,185 patients were enrolled. For TILs subsets, the amount of CD8+, FOXP3+, CD3+, CD57+, CD20+, CD45RO+, Granzyme B+ and T-bet+ lymphocytes was significantly associated with improved survival (P < 0.05); moreover, the amount of CD3+ TILs in intra-tumoral compartment (IT) was the most significant prognostic marker (pooled HR = 0.52; 95% CI = 0.43–0.63; P < 0.001). However, CD4+ TILs was not statistically associated with patients’ survival. FOXP3+ TILs showed bidirectional prognostic roles which had positive effect in IT (pooled HR = 1.57; 95% CI = 1.04–2.37; P = 0.033) and negative effect in extra-tumoral compartment (ET) (pooled HR = 0.76; 95% CI = 0.60–0.96; P = 0.022). Conclusions This meta-analysis suggests that some TIL subsets could serve as prognostic biomarkers in gastric cancer. High-quality randomized controlled trials are needed to decide if these TILs could serve as targets for immunotherapy in gastric cancer. PMID:28915679

A comprehensive characterization of simple sequence repeats in pepper genomes provides valuable resources for marker development in Capsicum.

PubMed

Cheng, Jiaowen; Zhao, Zicheng; Li, Bo; Qin, Cheng; Wu, Zhiming; Trejo-Saavedra, Diana L; Luo, Xirong; Cui, Junjie; Rivera-Bustamante, Rafael F; Li, Shuaicheng; Hu, Kailin

2016-01-07

The sequences of the full set of pepper genomes including nuclear, mitochondrial and chloroplast are now available for use. However, the overall of simple sequence repeats (SSR) distribution in these genomes and their practical implications for molecular marker development in Capsicum have not yet been described. Here, an average of 868,047.50, 45.50 and 30.00 SSR loci were identified in the nuclear, mitochondrial and chloroplast genomes of pepper, respectively. Subsequently, systematic comparisons of various species, genome types, motif lengths, repeat numbers and classified types were executed and discussed. In addition, a local database composed of 113,500 in silico unique SSR primer pairs was built using a homemade bioinformatics workflow. As a pilot study, 65 polymorphic markers were validated among a wide collection of 21 Capsicum genotypes with allele number and polymorphic information content value per marker raging from 2 to 6 and 0.05 to 0.64, respectively. Finally, a comparison of the clustering results with those of a previous study indicated the usability of the newly developed SSR markers. In summary, this first report on the comprehensive characterization of SSR motifs in pepper genomes and the very large set of SSR primer pairs will benefit various genetic studies in Capsicum.

A comprehensive characterization of simple sequence repeats in pepper genomes provides valuable resources for marker development in Capsicum

PubMed Central

Cheng, Jiaowen; Zhao, Zicheng; Li, Bo; Qin, Cheng; Wu, Zhiming; Trejo-Saavedra, Diana L.; Luo, Xirong; Cui, Junjie; Rivera-Bustamante, Rafael F.; Li, Shuaicheng; Hu, Kailin

2016-01-01

The sequences of the full set of pepper genomes including nuclear, mitochondrial and chloroplast are now available for use. However, the overall of simple sequence repeats (SSR) distribution in these genomes and their practical implications for molecular marker development in Capsicum have not yet been described. Here, an average of 868,047.50, 45.50 and 30.00 SSR loci were identified in the nuclear, mitochondrial and chloroplast genomes of pepper, respectively. Subsequently, systematic comparisons of various species, genome types, motif lengths, repeat numbers and classified types were executed and discussed. In addition, a local database composed of 113,500 in silico unique SSR primer pairs was built using a homemade bioinformatics workflow. As a pilot study, 65 polymorphic markers were validated among a wide collection of 21 Capsicum genotypes with allele number and polymorphic information content value per marker raging from 2 to 6 and 0.05 to 0.64, respectively. Finally, a comparison of the clustering results with those of a previous study indicated the usability of the newly developed SSR markers. In summary, this first report on the comprehensive characterization of SSR motifs in pepper genomes and the very large set of SSR primer pairs will benefit various genetic studies in Capsicum. PMID:26739748

Interleukin-8 is a prognostic indicator in human hilar cholangiocarcinoma

PubMed Central

Sun, Qi; Li, Fanni; Sun, Fengkai; Niu, Jun

2015-01-01

Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and neovascularization have been implicated to be associated with biological processes, especially cancer progression. However, few studies have investigated the role of IL-8 in human hilar cholangiocarcinoma. In this study we detected the expression of IL-8 combined with MMP-9 and microvessel density (MVD) in hilar cholangiocarcinoma to evaluate their clinicopathological significance and prognostic value. A total of 62 patients with hilar cholangiocarcinoma who underwent curative surgery were enrolled in this study. The expression of IL-8, MMP-9 and MVD were examined immunohistochemically. The correlation of IL-8 with MMP-9 expression, MVD, clinicopathological features and survival time of patients were then analyzed. Expression of IL-8 was observed in 56.5% tumors, which was related to advanced TNM stage (P = 0.026) and tumor recurrence (P = 0.018). IL-8 had a positive correlation with MMP-9 expression and MVD. Furthermore, patients with high IL-8 expression had a significantly shorter overall survival than those with low IL-8 expression (P = 0.01). Multivariate analysis confirmed IL-8 as an independent prognostic factor (P = 0.005). In conclusion, IL-8 expression significantly correlated with MMP-9 expression and MVD, and IL-8 was a valuable prognostic factor for human hilar cholangiocarcinoma. PMID:26339407

PTK 7 Is a Transforming Gene and Prognostic Marker for Breast Cancer and Nodal Metastasis Involvement

PubMed Central

Knyazeva, Tatiana; Wolf, Petra; Högel, Bernhard; Eiermann, Wolfgang; Ullrich, Axel; Knyazev, Pjotr; Ataseven, Beyhan

2014-01-01

Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance. PMID:24409301

Prognostics for Microgrid Components

NASA Technical Reports Server (NTRS)

Saxena, Abhinav

2012-01-01

Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

Prognostic and clinicopathological significance of CCAT2 in Chinese patients with various tumors.

PubMed

Tian, Guang-Wei; Li, Nan; Xin, Yan

2017-07-24

Colon cancer-associated transcript 2 (CCAT2) as a long noncoding RNA (lncRNA) is overexpressed and plays a significant prognostic role in patients with tumors. The present study aimed to comprehensively evaluate the clinical value of CCAT2 in the Chinese population, as a potential prognostic marker in multiple cancers. A systematic search of eligible studies was conducted in the PubMed, Web of Science, Cochrane Library, Wanfang and the China National Knowledge Infrastructure databases as of March 31, 2017. Approximately 1,711 tumor patients from 16 eligible studies were selected. Analyses of the pooled data were performed, and the odds ratio (OR) or hazard ratio (HR) and the 95% confidence interval (95% CI) were calculated and summarized to evaluate the strength of this association using a fixed- or random-effects model. Overall analyses showed that increased CCAT2 expression was associated with a higher risk of lymph node metastasis (LNM), an increased potential for distant metastasis (DM) and higher clinical stage (p<0.001 for LNM, p = 0.001 for DM, p<0.001 for clinical stage). HR and the 95% CI for overall survival (OS) were assessed to pool the effect size using a fixed-effects model. A significant association was observed between increased CCAT2 expression and poor OS (pooled HR = 1.91, 95% CI, 1.63-2.22, p<0.001). These results indicate that CCAT2 is a biomarker to predict tumor progression and a potential prognostic marker in multiple cancers. Additional well-designed clinical studies are needed to validate these findings.

Evaluation of desmin as a diagnostic and prognostic marker of childhood rhabdomyosarcomas and embryonal sarcomas.

PubMed Central

Dias, P.; Kumar, P.; Marsden, H. B.; Morris-Jones, P. H.; Birch, J.; Swindell, R.; Kumar, S.

1987-01-01

The diagnostic and prognostic relevance of desmin expression in 80 rhabdomyosarcomas (RMS) and 5 embryonal sarcomas (ES) was examined using a peroxidase anti-peroxidase staining procedure. Fifty-nine RMS but only one ES stained for desmin (P less than 0.05). The maximum percentage of desmin containing cells was 49 in RMS compared with only 1% in ES. Desmin positivity correlated inversely with survival (P less than 0.02) in that RMS with high proportions of desmin positive cells were associated with poorer prognoses than those containing fewer desmin positive cells. If the degree of expression of desmin is related to myogenic differentiation, then our results indicate that poorly differentiated RMS tend to have a better prognosis than the well differentiated tumours. One possible explanation is that the poorly differentiated RMS respond better to chemotherapy than to well differentiated RMS. A multivariant analysis incorporating desmin staining, treatment, histology, age and gender revealed that the two most significant independent prognostic factors were treatment and histology. Images Figure 1 PMID:3311112

Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma.

PubMed

Hwang, Ilseon; Kang, Yu Na; Kim, Jin Young; DO, Young Rok; Song, Hong Suk; Park, Keon Uk

2012-08-01

Aberrant expression of mucins is likely associated with cancer biology as alterations in the expression and/or glycosylation patterns of various mucins have been noted. Expression of the mucin family in gastric cancers has been reported in numerous studies, but the results are conflicting. Therefore, we investigated the potential use of mucin (MUC)1 and 4 as prognostic markers in gastric cancer according to histological subtype. Three-hundred and sixty-five gastric adenocarcinoma patients who underwent surgical resection were selected for this study. Among the 365 gastric cancer samples tested here, 34% consisted of early gastric cancer and 66% were advanced. In terms of location, 68.7% of the cohort had intestinal-type cancer and 30.7% had diffuse-type. We constructed tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using monoclonal antibodies. Two-hundred and ninety-two patients (92.7%) were positive for MUC1 and 216 (60.5%) were positive for MUC4. MUC1 expression was not correlated with any other clinicopathological variables such as age, gender, depth of invasion, lymph node metastasis, Lauren classification or recurrence. However, loss of MUC4 expression was significantly correlated with recurrence (p=0.033). MUC4 expression was also significantly correlated with better disease-free survival (p=0.049) and particularly in the intestinal-type (p=0.018). Our present findings demonstrated that loss of MUC4 expression can be used as a prognostic marker in gastric cancer. Loss of MUC4 expression is a prognostic indicator of increased recurrence and poor disease-free survival in patients with gastric cancer.

Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers.

PubMed

Luz, Maria Cláudia de B; Perez, Matheus M; Azzalis, Ligia A; Sousa, Luiz Vinícius de A; Adami, Fernando; Fonseca, Fernando L A; Alves, Beatriz da C A

2017-03-23

Patients with breast cancer-the deadliest cancer among women-are at constant risk of developing metastasis. Oxidative stress and hypoxia are common feature of tumor cells that can proliferate even in a resultant metabolic acidosis. Despite the low extracellular pH, intracellular pH of tumor cells remains relatively normal, or even more alkaline due to the action of a membrane protein family known as monocarboxylate transporters (MCTs). The objective of this study was to verify the diagnostic and prognostic value of MCT1 , MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic treatment. Differential expression of MCT1 , MCT4 and CD147 obtained by qPCR was determined by 2 -ΔΔ C q method between biological samples (tumor and serial samples of peripheral) of patients ( n = 125) and healthy women ( n = 25). tumor samples with higher histological grades have shown higher expression of these markers; this higher expression was also observed in blood samples obtained at diagnosis of patients when compared to healthy women and in patients with positive progression of the disease (metastasis development). markers studied here could be a promising strategy in routine laboratory evaluations as breast cancer diagnosis and prognosis.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma.

PubMed

Karsy, Michael; Neil, Jayson A; Guan, Jian; Mahan, Mark A; Mark, Mahan A; Colman, Howard; Jensen, Randy L

2015-03-01

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

[Immunological Markers in Organ Transplantation].

PubMed

Beckmann, J H; Heits, N; Braun, F; Becker, T

2017-04-01

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PubMed

Schernberg, Antoine; Huguet, Florence; Moureau-Zabotto, Laurence; Chargari, Cyrus; Rivin Del Campo, Eleonor; Schlienger, Michel; Escande, Alexandre; Touboul, Emmanuel; Deutsch, Eric

2017-07-01

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

PubMed

Martinez, Leandro Marcelo; Labovsky, Vivian; Calcagno, María de Luján; Davies, Kevin Mauro; Rivello, Hernán Garcia; Wernicke, Alejandra; Calvo, Juan Carlos; Chasseing, Norma Alejandra

2016-04-01

Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

PubMed

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Tejero, R; Díaz, T; Pratcorona, M; Tormo, M; Ribera, J M; Escoda, L; Duarte, R; Gallardo, D; Heras, I; Queipo de Llano, M P; Bargay, J; Monzo, M; Sierra, J; Navarro, A; Esteve, J

2014-04-01

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

PubMed

Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

2017-08-01

Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

Periostin is identified as a putative metastatic marker in breast cancer-derived exosomes

PubMed Central

Vardaki, Ioulia; Ceder, Sophia; Rutishauser, Dorothea; Baltatzis, George; Foukakis, Theodoros; Panaretakis, Theocharis

2016-01-01

Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines. We found significant differences not only in the amount of secreted exosomes but most importantly in the protein content of exosomes secreted from metastatic versus non-metastatic ones. We identified periostin as a protein that is enriched in exosomes secreted by metastatic cells and validated its presence in a pilot cohort of breast cancer patient samples with localized disease or lymph node (LN) metastasis. PMID:27589561

Periostin is identified as a putative metastatic marker in breast cancer-derived exosomes.

PubMed

Vardaki, Ioulia; Ceder, Sophia; Rutishauser, Dorothea; Baltatzis, George; Foukakis, Theodoros; Panaretakis, Theocharis

2016-11-15

Breast cancer (BrCa) is the most frequent cancer type in women and a leading cause of cancer related deaths in the world. Despite the decrease in mortality due to better diagnostics and palliative care, there is a lack of prognostic markers of metastasis. Recently, the exploitation of liquid biopsies and in particular of the extracellular vesicles has shown promise in the identification of such prognostic markers. In this study we compared the proteomic content of exosomes derived from metastatic and non-metastatic human (MCF7 and MDA-MB-231) and mouse (67NR and 4T1) cell lines. We found significant differences not only in the amount of secreted exosomes but most importantly in the protein content of exosomes secreted from metastatic versus non-metastatic ones. We identified periostin as a protein that is enriched in exosomes secreted by metastatic cells and validated its presence in a pilot cohort of breast cancer patient samples with localized disease or lymph node (LN) metastasis.

Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic

PubMed Central

Hendrickson, Andrea Wahner; Hawthorne, Kieran M.; Goode, Ellen L.; Kalli, Kimberly R.; Goergen, Krista M.; Bakkum-Gamez, Jamie N.; Cliby, William A.; Keeney, Gary L.; Visscher, Dan W.; Tarabishy, Yaman; Oberg, Ann L.; Hartmann, Lynn C.; Maurer, Matthew J.

2015-01-01

Objectives Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables. Methods Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000-2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset. Results Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results is suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking. Conclusions Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remain the most important predictors of prognosis in this setting. PMID:25620544

Retention of external and internal markers by southern pine beetles (Coleoptera: Scolytidae) during gallery

Treesearch

Douglas J. Rhodes; Jane Leslie Hayes; Chris Steiner

1998-01-01

If retained, markers used in mark-release-recapture studies of bark beetle dispersal could provide valuable tools in the determination of post-dispersal fate. Retention of the internal marker rubidium (Rb) and of the external marker fluorescent powder during egg gallery construction, oviposition, and feeding were quantified at intervals from 0 to 96 hours by allowing...

Gliomatosis cerebri: Prognosis based on current molecular markers.

PubMed

Maharaj, Monish M; Phan, Kevin; Xu, Joshua; Fairhall, Jacob; Reddy, Rajesh; Rao, Prashanth J V

2017-09-01

This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and identify outstanding markers requiring further study. A literature search was conducted across 5 major databases using the key terms: "Molecular markers" AND "Gliomatosis cerebri" OR "diffuse astrocytoma." Critical appraisal and data presentation was performed inline with the PRISMA guidelines. Following search strategy implementation, 11 studies were included in the final review process. Our data demonstrates significant prognostic value associated with IDH1 132H mutation and variable evidence surrounding the role of INA expression, MGMT promoter methylation and other factors. However, there are significant limitations in the level of evidence obtained. As the genetic basis for the pathogenesis of Gliomatosis cerebri continues to widen, there is little data on markers aside from IDH1 mutation available. IDH1 132H mutation has been demonstrated to have significant effect on survival, particularly in patients with Gliomatosis cerebri type 2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic roles of pathology markers immunoexpression and clinical parameters in Hepatoblastoma.

PubMed

Wu, Jia-Feng; Chang, Hsiu-Hao; Lu, Meng-Yao; Jou, Shiann-Tarng; Chang, Kai-Chi; Ni, Yen-Hsuan; Chang, Mei-Hwei

2017-08-29

Hepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells. We aimed to elucidate the relationships between the histological distribution of β-catenin and hepatic stem cell markers with the clinical outcomes of hepatoblastoma. Immunohistochemistry was applied to detect β-catenin and hepatic stem cell markers expression in 31 hepatoblastoma tumors. We analyzed the relationship between the stem cell markers and the clinical course of hepatoblastoma. Thirty-one hepatoblastoma patients were diagnosed at a mean age of 2.58 ± 3.78 years, and 7 (22.58%) died. A lack of anticipated decrease in alpha-fetal protein levels after neoadjuvant chemotherapy indicated a higher mortality rate. Nuclear β-catenin expression was significantly associated with membranous epithelial cell adhesion molecule (EpCAM) expression in hepatoblastoma tumor specimens. The co-expression of nuclear β-catenin and membranous EpCAM together with an age at diagnosis ≤1.25 years were predictive of an alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy (P < 0.05). An alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy and age at hepatoblastoma diagnosis ≤1.25 years are both predictors of better overall and native liver survival in hepatoblastoma patients. Presence of membranous EpCAM with nuclear β-catenin and younger diagnostic age of hepatoblastoma are predictive of serum alpha-fetoprotein levels drop after chemotherapy. Younger diagnostic age and lower alpha-fetoprotein levels after neoadjuvant chemotherapy and are predictive of better overall and native liver survival in hepatoblastoma patients.

Serum markers for prostate cancer: a rational approach to the literature.

PubMed

Steuber, Thomas; O'Brien, Matthew Frank; Lilja, Hans

2008-07-01

Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongly implicated to occur. Using current recommended guidelines, the PSA test suffers from both limited sensitivity and specificity to enable efficacious population-based cancer detection. Therefore, novel biomarkers are much needed to complement PSA by enhancing its diagnostic and prognostic performance. The present literature on serum markers for PCa was reviewed. PSA derivatives, molecular PSA isoforms, and novel molecular targets in blood were summarized and weighted against their potential to improve decision-making of men with PCa. Current evidence suggests that no single analyte is likely to achieve the desired level of diagnostic and prognostic accuracy for PCa. However, the combination of biomarkers with clinical and demographic data, for example, using established standard nomograms, has produced progress toward the goal of both optimal screening and risk assessment. Furthermore, potential candidate molecular markers for PCa can be derived from high-throughput technologies. Current studies demonstrate that understanding dynamic PSA changes over time may offer diagnostic and prognostic information. Bridging the gap between basic science and clinical practice represents the main goal in the near future to enable physicians to tailor risk-adjusted screening and treatment strategies for current patients with PCa.

Prognostic Value of Right Ventricular Dysfunction Markers for Serious Adverse Events in Acute Normotensive Pulmonary Embolism.

PubMed

Weekes, Anthony J; Johnson, Angela K; Troha, Daniel; Thacker, Gregory; Chanler-Berat, Jordan; Runyon, Michael

2017-02-01

Right ventricular dysfunction (RVD) in pulmonary embolism (PE) has been associated with increased morbidity. Tools for RVD identification are not well defined. The prognostic value of RVD markers to predict serious adverse events (SAE) during hospitalization is unclear. Prospectively compare the incidence of SAE in normotensive emergency department patients with PE based upon RVD by goal-directed echocardiography (GDE), cardiac biomarkers, and right-to-left ventricle ratio by computed tomography (CT). Simplified Pulmonary Embolism Severity Index (sPESI) was calculated. Deaths and readmissions within 30 days were recorded. Consecutive normotensive PE patients underwent GDE focused on RVD (RV enlargement, hypokinesis, or septal bowing), serum troponin, and brain natriuretic peptide (BNP), and evaluation of the CT ventricle ratio. In-hospital SAE and complications within 30 days were recorded. We enrolled 123 normotensive PE patients (median age 59 years, 49% female). Twenty-six of 123 (26%) patients had one or more SAE. RVD was detected in 26% by GDE, in 39% by biomarkers, and in 38% with CT. In-hospital SAE included one death, six respiratory interventions, six dysrhythmias, three major bleeding episodes, and 21 hypotension episodes. Forty-one percent of patients RVD positive by GDE had SAE, compared to the 18% RVD negative by GDE. Odds ratios for GDE, CT, BNP, troponin, and sPESI for SAE were 3.2 (95% confidence interval [CI] 1.2-8.5), 2.0 (95% CI 0.8-5.1), 3.3 (95% CI 1.3-8.6), 4.2 (95% CI 1.4-13.5), and 2.9 (95% CI 1.1-8.3), respectively. Five patients had non-PE-related deaths within 30 days. The incidence of SAE within days of PE was significant in our cohort. Those with RVD had an increased risk of nonmortality SAE. Copyright © 2016 Elsevier Inc. All rights reserved.

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

PubMed Central

Jonsdottir, Ingibjörg H.; Hägg, Daniel A.; Glise, Kristina; Ekman, Rolf

2009-01-01

Background Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. Methodology/Principal Findings Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients. Conclusions/Significance MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured. PMID:19888340

Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration

PubMed Central

Nosrati, Mehdi; Tong, Schuyler; Wu, Clayton; Thummala, Suresh; Dar, Altaf A.; Leong, Stanley P.L.; Cleaver, James E.; Sagebiel, Richard W.; Miller, James R.; Kashani-Sabet, Mohammed

2013-01-01

Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. PMID:24005052

Diagnostic/prognostic molecular cytogenetic follow-up applied in satellited marker cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papenhausen, P.R.; Anderson, S.

1994-09-01

Special caution needs to be exercised in offering a good prognosis in Prader-Willi probe negative 15-derived marker cases, since it is clear that phenotypic effects can still be associated with the apparent presence of proximal sequences. We have had two postnatal cases in this category, one which was inherited from an unaffected paternal (non-mosaic) carrier, possibly demonstrating imprinting effects. Familial studies are continuing in this case. Although the D22/S9 locus appears diagnostic of cateye syndrome (CES), the dual specificity of the 14/22 centromeric probe leaves the possibility of a poor prognosis 14 derivation when the CES probe is negative. Therefore,more » it is imperative that proximal long arm 13, 14, 21 and more proximal 15 FISH probes be implemented so that a phenotypically correlated database may indicate the proper FISH probes necessary for accurate prognosis. Bisatellited markers is which a bipartite centromeric probe signal was found were considered to be higher risk than those with the single signal in counseling.« less

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium.

PubMed

Stevens, Wendy B C; Mendeville, Matias; Redd, Robert; Clear, Andrew J; Bladergroen, Reno; Calaminici, Maria; Rosenwald, Andreas; Hoster, Eva; Hiddemann, Wolfgang; Gaulard, Philippe; Xerri, Luc; Salles, Gilles; Klapper, Wolfram; Pfreundschuh, Michael; Jack, Andrew; Gascoyne, Randy D; Natkunam, Yasodha; Advani, Ranjana; Kimby, Eva; Sander, Birgitta; Sehn, Laurie H; Hagenbeek, Anton; Raemaekers, John; Gribben, John; Kersten, Marie José; Ylstra, Bauke; Weller, Edie; de Jong, Daphne

2017-08-01

In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years versus long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type ( P =0.006), gain of chromosome 18 ( P =0.002), low percentages of CD8+ cells ( P =0.011) and CD163+ areas ( P =0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers. Copyright© 2017 Ferrata Storti Foundation.

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

PubMed Central

Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

2015-01-01

Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

Early prognostic markers for fatal fulminant hepatic failure cases with viral hepatitis: proton nuclear magnetic resonance spectroscopic studies of serum.

PubMed

Bala, Lakshmi; Mehrotra, Mayank; Mohindra, Samir; Saxena, Rajan; Khetrapal, Chunni Lal

2013-02-01

Fulminant hepatic failure is associated with liver metabolic derangements which could have fatal consequences. The aim of the present study is to identify serum markers for early prediction of the outcome. Proton nuclear magnetic resonance spectroscopic studies of serum of fulminant hepatic failure patients due to viral hepatitis with grade II/III of encephalopathy (twenty-four: ten prospective and fourteen retrospective) and twenty-five controls were undertaken. Of the twenty-four patients, fifteen survived with medical management alone while nine had fatal outcome. The results demonstrated significantly elevated indices of amino acids (alanine, lysine, glutamine, histidine, tyrosine, phenylalanine and 1,2-propanediol) in fatal cases compared to survivors and controls. Principal component analysis showed clear separation of fatal and surviving cases. Liver function parameters were significantly deranged in patients but they failed to provide early significant differences between surviving and fatal cases. Compared to model for end-stage liver disease scores, principal component analysis appear to be better as an early prognostic indicator. Biochemical mapping of pathways suggested interruptions in amino acid metabolism and urea cycle. Proton nuclear magnetic resonance studies of serum have the potential of rapidly identifying patients with irreversible fulminant hepatic failure requiring liver transplantation as life saving option. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification.

PubMed

Bu, Jiyoung; Youn, Sangmin; Kwon, Wooil; Jang, Kee Taek; Han, Sanghyup; Han, Sunjong; You, Younghun; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook

2018-02-01

Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades ( p <0.001, and p <0.001). Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy

PubMed Central

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-01-01

Abstract Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients. A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3–60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%). In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31–1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86–3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS. In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients. PMID:26496339

Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

PubMed

Khatri, Vinod; Neal, Jennifer E; Burger, Charles D; Lee, Augustine S

2015-02-06

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Although multiple SET variables correlated with the RRRS on univariate analyses, only V E /V CO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the V E /V CO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). SETs, particularly the V E /V CO2 , appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer.

PubMed

Kano, Satoshi; Homma, Akihiro; Hatakeyama, Hiromitsu; Mizumachi, Takatsugu; Sakashita, Tomohiro; Kakizaki, Tomohiko; Fukuda, Satoshi

2017-02-01

The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017. © 2016 Wiley Periodicals, Inc.

A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma.

PubMed

Stewart, Paul A; Parapatics, Katja; Welsh, Eric A; Müller, André C; Cao, Haoyun; Fang, Bin; Koomen, John M; Eschrich, Steven A; Bennett, Keiryn L; Haura, Eric B

2015-01-01

We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma. Data are available via ProteomeXchange with identifier PXD002622.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

PubMed

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis

PubMed Central

Luo, Fei; Wang, Ya-Shen; Su, Yan-Hui; Zhang, Zhi-Hua; Sun, Hong-Hong; Li, Jian

2017-01-01

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83–2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59–2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76–2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction. PMID:28182725

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

PubMed

Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

2014-10-20

The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

Development of Novel Microsatellite Markers for the BBCC Oryza Genome (Poaceae) Using High-Throughput Sequencing Technology

PubMed Central

Peng, Suotang; Xu, Qun; Yuan, Xiaoping; Feng, Yue; Yu, Hanyong; Wang, Yiping; Wei, Xinghua

2014-01-01

Wild species of Oryza are extremely valuable sources of genetic material that can be used to broaden the genetic background of cultivated rice, and to increase its resistance to abiotic and biotic stresses. Until recently, there was no sequence information for the BBCC Oryza genome; therefore, no special markers had been developed for this genome type. The lack of suitable markers made it difficult to search for valuable genes in the BBCC genome. The aim of this study was to develop microsatellite markers for the BBCC genome. We obtained 13,991 SSR-containing sequences and designed 14,508 primer pairs. The most abundant was hexanuclelotide (31.39%), followed by trinucleotide (27.67%) and dinucleotide (19.04%). 600 markers were selected for validation in 23 accessions of Oryza species with the BBCC genome. A set of 495 markers produced clear amplified fragments of the expected sizes. The average number of alleles per locus (Na) was 2.5, ranging from 1 to 9. The genetic diversity per locus (He) ranged from 0 to 0.844 with a mean of 0.333. The mean polymorphism information content (PIC) was 0.290, and ranged from 0 to 0.825. Of the 495 markers, 12 were only found in the BB genome, 173 were unique to the CC genome, and 198 were also present in the AA genome. These microsatellite markers could be used to evaluate the phylogenetic relationships among different Oryza genomes, and to construct a genetic linkage map for locating and identifying valuable genes in the BBCC genome, and would also for marker-assisted breeding programs that included accessions with the AA genome, especially Oryza sativa. PMID:24632997

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma

PubMed Central

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-01-01

Background In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). Material/Methods Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. Results 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123–6.760, p=0.027). Conclusions The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC. PMID:28779068

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma.

PubMed

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-08-05

BACKGROUND In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). MATERIAL AND METHODS Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. RESULTS 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123-6.760, p=0.027). CONCLUSIONS The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC.

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

PubMed

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Next generation DNA sequencing technology delivers valuable genetic markers for the genomic orphan legume species, Bituminaria bituminosa

PubMed Central

2011-01-01

Background Bituminaria bituminosa is a perennial legume species from the Canary Islands and Mediterranean region that has potential as a drought-tolerant pasture species and as a source of pharmaceutical compounds. Three botanical varieties have previously been identified in this species: albomarginata, bituminosa and crassiuscula. B. bituminosa can be considered a genomic 'orphan' species with very few genomic resources available. New DNA sequencing technologies provide an opportunity to develop high quality molecular markers for such orphan species. Results 432,306 mRNA molecules were sampled from a leaf transcriptome of a single B. bituminosa plant using Roche 454 pyrosequencing, resulting in an average read length of 345 bp (149.1 Mbp in total). Sequences were assembled into 3,838 isotigs/contigs representing putatively unique gene transcripts. Gene ontology descriptors were identified for 3,419 sequences. Raw sequence reads containing simple sequence repeat (SSR) motifs were identified, and 240 primer pairs flanking these motifs were designed. Of 87 primer pairs developed this way, 75 (86.2%) successfully amplified primarily single fragments by PCR. Fragment analysis using 20 primer pairs in 79 accessions of B. bituminosa detected 130 alleles at 21 SSR loci. Genetic diversity analyses confirmed that variation at these SSR loci accurately reflected known taxonomic relationships in original collections of B. bituminosa and provided additional evidence that a division of the botanical variety bituminosa into two according to geographical origin (Mediterranean region and Canary Islands) may be appropriate. Evidence of cross-pollination was also found between botanical varieties within a B. bituminosa breeding programme. Conclusions B. bituminosa can no longer be considered a genomic orphan species, having now a large (albeit incomplete) repertoire of expressed gene sequences that can serve as a resource for future genetic studies. This experimental approach was

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

PubMed

Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

2012-09-13

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

A Generic Software Architecture For Prognostics

NASA Technical Reports Server (NTRS)

Teubert, Christopher; Daigle, Matthew J.; Sankararaman, Shankar; Goebel, Kai; Watkins, Jason

2017-01-01

Prognostics is a systems engineering discipline focused on predicting end-of-life of components and systems. As a relatively new and emerging technology, there are few fielded implementations of prognostics, due in part to practitioners perceiving a large hurdle in developing the models, algorithms, architecture, and integration pieces. As a result, no open software frameworks for applying prognostics currently exist. This paper introduces the Generic Software Architecture for Prognostics (GSAP), an open-source, cross-platform, object-oriented software framework and support library for creating prognostics applications. GSAP was designed to make prognostics more accessible and enable faster adoption and implementation by industry, by reducing the effort and investment required to develop, test, and deploy prognostics. This paper describes the requirements, design, and testing of GSAP. Additionally, a detailed case study involving battery prognostics demonstrates its use.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

PubMed

Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

2016-09-01

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

PubMed Central

Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes

2018-01-01

The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC. PMID:29682178

Prognostic value of circulating microRNAs in upper tract urinary carcinoma.

PubMed

Montalbo, Ruth; Izquierdo, Laura; Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes

2018-03-30

The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.

Long Non-Coding RNAs As Potential Novel Prognostic Biomarkers in Colorectal Cancer

PubMed Central

Saus, Ester; Brunet-Vega, Anna; Iraola-Guzmán, Susana; Pegueroles, Cinta; Gabaldón, Toni; Pericay, Carles

2016-01-01

Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Surgery is usually the first line of treatment for patients with CRC but many tumors with similar histopathological features show significantly different clinical outcomes. The discovery of robust prognostic biomarkers in patients with CRC is imperative to achieve more effective treatment strategies and improve patient's care. Recent progress in next generation sequencing methods and transcriptome analysis has revealed that a much larger part of the genome is transcribed into RNA than previously assumed. Collectively referred to as non-coding RNAs (ncRNAs), some of these RNA molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to be altered and to play critical roles in tumor biology. This discovery leads to exciting possibilities for personalized cancer diagnosis, and therapy. Many lncRNAs are tissue and cancer-type specific and have already revealed to be useful as prognostic markers. In this review, we focus on recent findings concerning aberrant expression of lncRNAs in CRC tumors and emphasize their prognostic potential in CRC. Further studies focused on the mechanisms of action of lncRNAs will contribute to the development of novel biomarkers for diagnosis and disease progression. PMID:27148353

Prognostic significance of FAM83D gene expression across human cancer types

DOE PAGES

Walian, Peter J.; Hang, Bo; Mao, Jian-Hua

2015-12-15

The family with sequence similarity 83, member D (FAM83D) gene has been proposed as a new prognostic marker for breast cancer. In this work, we further evaluate the prognostic significance of FAM83D expression in different breast cancer subtypes using a meta-analysis. Patients with higher FAM83D mRNA levels have significantly decreased overall and metastatic relapse-free survival, particularly in the group of patients with ER-positive, or luminal subtype tumors. We also assessed FAM83D alterations and its prognostic significance across 22 human cancer types using The Cancer Genome Atlas (TCGA). FAM83D is frequently gained in the majority of human cancer types, resulting inmore » the elevated expression of FAM83D. Higher levels of FAM83D mRNA expression are significantly associated with decreased overall survival in several cancer types. Finally, we demonstrate that TP53 mutation in human cancers is coupled to a significant increase in the expression of FAM83D, and that a higher level of FAM83D expression is positively correlated with an increase in genome instability in many cancer types. These results identify FAM83D as a potential novel oncogene across multiple human cancer types.« less

Prognostic Relevance of Lymph Node Regression After Neoadjuvant Chemoradiation for Esophageal Cancer.

PubMed

Philippron, Annouck; Bollschweiler, Elfriede; Kunikata, Ayumi; Plum, Patrick; Schmidt, Claudia; Favi, Francesco; Drebber, Uta; Hölscher, Arnulf H

2016-01-01

Prognostic factors after preoperative chemoradiation for patients with advanced esophageal cancer are under discussion. Treatment response measured in the primary tumor is a well-defined prognostic marker. The prognostic relevance of tumor regression in lymph nodes (LNs), eg, histomorphologic characteristics must be evaluated in a larger series of patients. From 1997-2010, 403 patients with cT3N×M0 esophageal cancer underwent preoperative chemoradiation followed by transthoracic esophagectomy. Histopathologic response of the primary tumor was graded in resected specimens as "minor" (≥10% vital residual tumor cells) or "major." The LNs of all patients without LN metastases (ypN0 n = 222, adenocarcinoma n = 129, squamous cell carcinoma n = 93) were reevaluated for central fibrosis. Univariate and multivariate analyses were performed on histomorphologic criteria of examined LNs and used to correlate these with tumor response and prognosis. The 5-year survival rate (5YSR) for all patients was 30%. Overall, 5480 LNs were reevaluated for the existence of central fibrosis in ypN0 cases. The prognostic relevance of the LN regression (LNR) grading system was confirmed for all patients with univariate (P < 0.001) and multivariate (P = 0.02) analyses. In results, the 5YSR for ypN0 patients overall was 37%, for patients with major response by the primary tumor was 42%, and for minor responders was 19% (P < 0.001). Analyzing LNR in major responders, the group with less than 3 LNs with central fibrosis (n = 52) showed significantly better prognosis (5YSR = 63%) compared to those with more (5YSR = 34%), (P = 0.016). Conclusion includes morphologic signs of metastatic LNR after chemoradiation, such as central fibrosis, are of prognostic relevance for patients with advanced esophageal cancer, especially for those with major response of the primary tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment.

PubMed

Gluz, Oleg; Nitz, Ulrike A; Christgen, Matthias; Kates, Ronald E; Shak, Steven; Clemens, Michael; Kraemer, Stefan; Aktas, Bahriye; Kuemmel, Sherko; Reimer, Toralf; Kusche, Manfred; Heyl, Volker; Lorenz-Salehi, Fatemeh; Just, Marianne; Hofmann, Daniel; Degenhardt, Tom; Liedtke, Cornelia; Svedman, Christer; Wuerstlein, Rachel; Kreipe, Hans H; Harbeck, Nadia

2016-07-10

The 21-gene Recurrence Score (RS) assay is a validated prognostic/predictive tool in early hormone receptor-positive breast cancer (BC); however, only a few prospective outcome results have been available so far. In the phase III PlanB trial, RS was prospectively used to define a subset of patients who received only endocrine therapy. We present 3-year outcome data and concordance analysis (among biomarkers/RS). Central tumor bank was established prospectively from PlanB (intermediate and high-risk, locally human epidermal growth factor receptor 2-negative BC). After an early amendment, HR-positive, pN0-1 patients with RS ≤ 11 were recommended to omit chemotherapy. From 2009 to 2011, PlanB enrolled 3,198 patients with a median age of 56 years; 41.1% had node-positive and 32.5% grade 3 disease. In 348 patients (15.3%), chemotherapy was omitted based on RS ≤ 11. After 35 months median follow-up, 3-year disease-free survival in patients with RS ≤ 11 and endocrine therapy alone was 98% versus 92% and 98% in RS > 25 and RS 12 to 25 in chemotherapy-treated patients, respectively. Nodal status, central and local grade, the Ki-67 protein encoded by the MKI67 gene, estrogen receptor, progesterone receptor, tumor size, and RS were univariate prognostic factors for disease-free survival; only nodal status, both central and local grade, and RS were independent multivariate factors. Histologic grade was discordant between central and local laboratories in 44%. RS was positively but moderately correlated with the Ki-67 protein encoded by the MKI67 gene and grade and negatively correlated with progesterone receptor and estrogen receptor. In this prospective trial, patients with enhanced clinical risk and omitted chemotherapy on the basis of RS ≤ 11 had excellent 3-year survival. The substantial discordance observed between traditional prognostic markers and RS emphasizes the need for standardized assessment and supports the potential integration of standardized, well

Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

PubMed

Weng, Ruihui; Wei, Xiaobo; Yu, Bin; Zhu, Shuzhen; Yang, Xiaohua; Xie, Fen; Zhang, Mahui; Jiang, Ying; Feng, Zhong-Ping; Sun, Hong-Shuo; Xia, Ying; Jin, Kunlin; Chan, Piu; Wang, Qing; Gao, Xiaoya

2018-07-01

Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity. We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects. Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter. Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP. Copyright © 2018 Elsevier Ltd. All rights reserved.

High expression of anti-apoptotic protein Bcl-2 is a good prognostic factor in colorectal cancer: Result of a meta-analysis.

PubMed

Huang, Qi; Li, Shu; Cheng, Pu; Deng, Mei; He, Xin; Wang, Zhen; Yang, Cheng-Hui; Zhao, Xiao-Ying; Huang, Jian

2017-07-21

To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer (CRC). A systematic literature search was conducted using PubMed, Web of Science and EMBASE databases. Any eligible study must meet the following criteria: (1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry; (2) assessment of the relationships between bcl-2 expression and overall survival (OS), disease free survival (DFS), recurrent free survival (RFS) or clinic-pathological characteristics of CRC was included; (3) sufficient information was provided to estimate the hazard ratio (HR) or odds ratio and their 95% confidence intervals (CIs); and (4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis. A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS (pooled HR = 0.69, 95%CI: 0.55-0.87, P = 0.002) and better DFS/RFS (pooled HR = 0.65, 95%CI: 0.50-0.85, P = 0.001). Additionally, the subgroup analysis suggested that Bcl-2 overexpression was significantly associated with prognosis (OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally, our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage. Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence, we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.

High expression of anti-apoptotic protein Bcl-2 is a good prognostic factor in colorectal cancer: Result of a meta-analysis

PubMed Central

Huang, Qi; Li, Shu; Cheng, Pu; Deng, Mei; He, Xin; Wang, Zhen; Yang, Cheng-Hui; Zhao, Xiao-Ying; Huang, Jian

2017-01-01

AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer (CRC). METHODS A systematic literature search was conducted using PubMed, Web of Science and EMBASE databases. Any eligible study must meet the following criteria: (1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry; (2) assessment of the relationships between bcl-2 expression and overall survival (OS), disease free survival (DFS), recurrent free survival (RFS) or clinic-pathological characteristics of CRC was included; (3) sufficient information was provided to estimate the hazard ratio (HR) or odds ratio and their 95% confidence intervals (CIs); and (4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis. RESULTS A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS (pooled HR = 0.69, 95%CI: 0.55-0.87, P = 0.002) and better DFS/RFS (pooled HR = 0.65, 95%CI: 0.50-0.85, P = 0.001). Additionally, the subgroup analysis suggested that Bcl-2 overexpression was significantly associated with prognosis (OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally, our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks’ stage. CONCLUSION Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence, we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC. PMID:28785155

C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study.

PubMed

Khan, Sohail Q; Dhillon, Onkar S; O'Brien, Russell J; Struck, Joachim; Quinn, Paulene A; Morgenthaler, Nils G; Squire, Iain B; Davies, Joan E; Bergmann, Andreas; Ng, Leong L

2007-04-24

The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction. In this prospective single-hospital study, we recruited 980 consecutive post-acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of approximately 900 pmol/L), copeptin above the median (approximately 7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points. The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than approximately 900 pmol/L).

Toward IVHM Prognostics

NASA Technical Reports Server (NTRS)

Walsh, Kevin; Venti, Mike

2007-01-01

This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

Astrocyte elevated gene-1: a novel independent prognostic biomarker for metastatic ovarian tumors.

PubMed

Li, Cong; Chen, Kexin; Cai, Jianping; Shi, Qing-Tao; Li, Yinghong; Li, Lejing; Song, Hongtao; Qiu, Huilei; Qin, Yu; Geng, Jing-Shu

2014-04-01

Astrocyte elevated gene-1 (AEG-1), a novel tumor-associated gene, was found overexpressed in many tumors. Therefore, our purpose is to estimate whether AEG-1 overexpression is a novel predictor of prognostic marker in metastatic ovarian tumors. Immunohistochemistry was used to estimate AEG-1 overexpression in metastatic ovarian tumors from 102 samples. The association between AEG-1 expression and prognosis was estimated by univariate and multivariate survival analyses with Cox regression. The log-rank test was used to identify any differences in the prognosis between the two groups. The median overall and progression-free survival rates of patients with tumors from gastrointestinal tract origin were 0.97 and 0.51 years, respectively. Similarly, survival rates of patients with tumors of breast origin were 2.68 and 1.96 years (P < 0.0001). Of 102 patients, 77 had high expression, and AEG-1 overexpression had a significant link of prognosis in metastatic ovarian patients (P < 0.01). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the tumors from gastrointestinal tract primary malignancies. It is suggested that AEG-1 overexpression might be an independent prognostic marker of metastatic ovarian tumors.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

PubMed

Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

2018-01-01

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding

PubMed Central

Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

2016-01-01

Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection. PMID:26799713

Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding.

PubMed

Fan, Wei; Zong, Jie; Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

2016-01-01

Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection.

The autophagy-related marker LC3 can predict prognosis in human hepatocellular carcinoma.

PubMed

Lee, Yoo Jin; Hah, Yu Jin; Ha, Yu Jin; Kang, Yu Na; Kang, Koo Jeong; Hwang, Jae Seok; Chung, Woo Jin; Cho, Kwang Bum; Park, Kyung Sik; Kim, Eun Soo; Seo, Hye-Young; Kim, Mi-Kyung; Park, Keun-Gyu; Jang, Byoung Kuk

2013-01-01

Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein. The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis. LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers. Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.

A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer.

PubMed

Pan, Qun-Xiong; Su, Zi-Jian; Zhang, Jian-Hua; Wang, Chong-Ren; Ke, Shao-Ying

2015-01-01

People's Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors. To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM) stage in patients undergoing gastric cancer resection. The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and prognostic index (PI) were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage. In univariate analysis, preoperative serum C-reactive protein (P<0.001), serum albumin (P<0.001), GPS (P<0.001), PLR (P=0.002), NLR (P<0.001), PI (P<0.001), PNI (P<0.001), and TNM stage (P<0.001) were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024), NLR (P=0.012), PI (P=0.001), TNM stage (P<0.001), and degree of differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating characteristic curve as compared to other

Clinicopathological Profiling of LC3B, an Autophagy Marker, and ESRRA (Estrogen-related Receptor-alpha) in Muscle-invasive Bladder Cancer.

PubMed

Kim, Sup; Lee, Adam Jaehyeok; Yeo, Min-Kyung; Na, Yong Gil; Kim, Ji-Yeon; Cho, Moon-June; Kim, Jun-Sang; Jo, Eun-Kyeong; Kim, Jin-Man

2018-04-01

Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

PubMed Central

Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

2016-01-01

Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

Practical prognostic index for patients with metastatic recurrent breast cancer: retrospective analysis of 2,322 patients from the GEICAM Spanish El Alamo Register.

PubMed

Puente, Javier; López-Tarruella, Sara; Ruiz, Amparo; Lluch, Ana; Pastor, Miguel; Alba, Emilio; de la Haba, Juan; Ramos, Manuel; Cirera, Luis; Antón, Antonio; Llombart, Antoni; Plazaola, Arrate; Fernández-Aramburo, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo; Martin, Miguel

2010-07-01

Women with recurrent metastatic breast cancer from a Spanish hospital registry (El Alamo, GEICAM) were analyzed in order to identify the most helpful prognostic factors to predict survival and to ultimately construct a practical prognostic index. The inclusion criteria covered women patients diagnosed with operable invasive breast cancer who had metastatic recurrence between 1990 and 1997 in GEICAM hospitals. Patients with stage IV breast cancer at initial diagnosis or with isolated loco-regional recurrence were excluded from this analysis. Data from 2,322 patients with recurrent breast cancer after primary treatment (surgery, radiation and systemic adjuvant treatment) were used to construct the prognostic index. The prognostic index score for each individual patient was calculated by totalling up the scores of each independent variable. The maximum score obtainable was 26.1. Nine-hundred and sixty-two patients who had complete data for all the variables were used in the computation of the prognostic index score. We were able to stratify them into three prognostic groups based on the prognostic index score: 322 patients in the good risk group (score < or =13.5), 308 patients in the intermediate risk group (score 13.51-15.60) and 332 patients in the poor risk group (score > or =15.61). The median survivals for these groups were 3.69, 2.27 and 1.02 years, respectively (P < 0.0001). In conclusion, risk scores are extraordinarily valuable tools, highly recommendable in the clinical practice.

The Shifting Paradigm of Prognostic Factors of Colorectal Liver Metastases: From Tumor-Centered to Host Immune-Centered Factors

PubMed Central

Donadon, Matteo; Lleo, Ana; Di Tommaso, Luca; Soldani, Cristiana; Franceschini, Barbara; Roncalli, Massimo; Torzilli, Guido

2018-01-01

The determinants of prognosis in patients with colorectal liver metastases (CLM) have been traditionally searched among the tumoral factors, either of the primary colorectal tumor or of the CLM. While many different scoring systems have been developed based on those clinic-pathological factors with disparate results, there has been the introduction of genetic biological markers that added a theranostic perspective. More recently, other important elements, such as those factors related to the host immune system, have been proposed as determinants of prognosis of CLM patients. In the present work, we review the current prognostic factors of CLM patients as well as the burgeoning shifting paradigm of prognostication that relies on the host immune system. PMID:29892573

Prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis.

PubMed

Maiwall, Rakhi; Kumar, Suman; Sharma, Manoj Kumar; Wani, Zeeshan; Ozukum, Mulu; Sarin, Shiv Kumar

2016-05-01

The prevalence and clinical significance of hyponatremia in cirrhotics have been well studied; however, there are limited data on hyperkalemia in cirrhotics. We evaluated the prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis and developed a prognostic model incorporating potassium for prediction of liver-related death in these patients. The training derivative cohort of patients was used for development of prognostic scores (Group A, n = 1160), which were validated in a large prospective cohort of cirrhotic patients. (Group B, n = 2681) of cirrhosis. Hyperkalemia was seen in 189 (14.1%) and 336 (12%) in Group A and Group B, respectively. Potassium showed a significant association that was direct with creatinine (P < 0.001) and urea (P < 0.001) and inverse with sodium (P < 0.001). Mortality was also significantly higher in patients with hyperkalemia (P = 0.0015, Hazard Ratio (HR) 1.3, 95% confidence interval 1.11-1.57). Combination of all these parameters into a single value predictor, that is, renal dysfunction index predicted mortality better than the individual components. Combining renal dysfunction index with other known prognostic markers (i.e. serum bilirubin, INR, albumin, hepatic encephalopathy, and ascites) in the "K" model predicted both short-term and long-term mortality with an excellent accuracy (Concordance-index 0.78 and 0.80 in training and validation cohorts, respectively). This was also superior to Model for End-stage Liver Disease, Model for End-stage liver disease sodium (MELDNa), and Child-Turcott-Pugh scores. Cirrhotics frequently have impaired potassium homeostasis, which has a prognostic significance. Serum potassium correlates directly with serum creatinine and urea and inversely with serum sodium. The model incorporating serum potassium developed from this study ("K"model) can predict death in advanced cirrhotics with an excellent accuracy. © 2015 Journal of

Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

PubMed Central

Banin Hirata, Bruna Karina; Oda, Julie Massayo Maeda; Losi Guembarovski, Roberta; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Watanabe, Maria Angelica Ehara

2014-01-01

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity. PMID:24591761

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Albumin and C-reactive protein have prognostic significance in patients with community-acquired pneumonia.

PubMed

Lee, Jae Hyuk; Kim, Jooyeong; Kim, Kyuseok; Jo, You Hwan; Rhee, JoongEui; Kim, Tae Youn; Na, Sang Hoon; Hwang, Seung Sik

2011-06-01

This study aims to determine the association of commonly used biochemical markers, such as albumin and C-reactive protein (CRP), with mortality and the prognostic performance of these markers combined with the pneumonia severity index (PSI) for mortality and adverse outcomes in patients with community-acquired pneumonia (CAP). The data were gathered prospectively for patients hospitalized with CAP via the emergency department. Laboratory values, including CRP and albumin, clinical variables, and the PSI were measured. Primary outcomes were 28-day mortality and survival times. Secondary outcome was admission to the intensive care unit, vasopressor use, or the need for mechanical ventilation during the hospital stay. A total of 424 patients were included. The 28-day mortality was 13.7%. C-reactive protein and albumin were significantly different between survivors and nonsurvivors. In logistic regression analysis, CRP and albumin were independently associated with 28-day mortality (P < .05). Receiver operating characteristic curves showed improved mortality prediction by adding CRP or albumin to the PSI scale. The Cox proportional hazards analysis showed that high serum albumin (≥3.3 mg/dL) had a hazard ratio of 0.5 (95% confidence interval, 0.3-0.9), and high CRP (≥14.3 mg/dL) had a hazard ratio of 2.0 (95% confidence interval, 1.1-3.4). For predicting secondary outcome, adding albumin to PSI increased areas under the curve significantly, but CRP did not. Albumin and CRP were associated with 28-day mortality in hospitalized patients with CAP, and these markers increased prognostic performance when combined with the PSI scale. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

PubMed

Melcarne, Luigi; Sopeña, Julia; Martínez-Cerezo, Francisco José; Vergara, Mercedes; Miquel, Mireia; Sánchez-Delgado, Jordi; Dalmau, Blai; Machlab, Salvador; Portilla, Dustin; González-Padrón, Yonaisy; Real Álvarez, Mónica; Carpintero, Chantal; Casas, Meritxell

2018-02-01

Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

PubMed Central

Exner, Ruth; Pulverer, Walter; Diem, Martina; Spaller, Lisa; Woltering, Laura; Schreiber, Martin; Wolf, Brigitte; Sonntagbauer, Markus; Schröder, Fabian; Stift, Judith; Wrba, Fritz; Bergmann, Michael; Weinhäusel, Andreas; Egger, Gerda

2015-01-01

Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. Results: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. Conclusions: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer. PMID:26335606

Development, genetic mapping and QTL association of cotton PHYA, PHYB, and HY5-specific CAPS and dCAPS markers

USDA-ARS?s Scientific Manuscript database

Among SNP markers that become increasingly valuable in molecular breeding of crop plants are the CAP and dCAP markers derived from the genes of interest. To date, the number of such gene-based markers is small in polyploid crop plants such as tetraploid cotton that has A and D subgenomes. The obje...

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

PubMed

Rostagno, Carlo; Olivo, Giuseppe; Comeglio, Marco; Boddi, Vieri; Banchelli, Michela; Galanti, Giorgio; Gensini, Gian Franco

2003-06-01

The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.

[Diagnostic (STARD) and prognostic (REMARK) studies].

PubMed

Altman, Douglas G; Bossuyt, Patrick Mm

2005-12-01

Deficiencies in how research studies are reported are both well-documented and widespread across all medical specialties and study designs. Although randomised trials have received the most attention in this regard, similar concerns have been expressed about reporting of other types of research including diagnostic and epidemiological studies. If a journal article describes in enough detail what was done at each stage of a study, readers will have enough information to allow them to decide on the merits of the results for themselves. From this simple idea comes the scientific rationale of developing guidelines on how to report research. Recommended processes to produce reporting guidelines have evolved over several years during the preparation of a sequence of reporting guidelines starting with CONSORT and QUOROM in the 1990s. We describe initiatives to develop reporting guidelines for diagnostic accuracy studies (STARD) and tumour marker prognostic studies (REMARK).

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

PubMed Central

Pallarès, Victor; Hoyos, Montserrat; Chillón, M. Carmen; Barragán, Eva; Conde, M. Isabel Prieto; Llop, Marta; Céspedes, María Virtudes; Nomdedeu, Josep F.; Brunet, Salut; Sanz, Miguel Ángel; González-Díaz, Marcos; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

2017-01-01

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients. PMID:29100287

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

PubMed

Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience.

PubMed

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-10-01

Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients.A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3-60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%).In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31-1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86-3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS.In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.

[Procalcitonin as a diagnostic marker in systemic inflammatory response syndrome (SIRS) and sepsis].

PubMed

Hryckiewicz, Katarzyna; Juszczyk, Jacek; Samet, Alfred; Arłukowicz, Elzbieta; Sledzińska, Anna; Bolewska, Beata

2006-01-01

Evaluation the value of procalcitonin as a diagnostic and prognostic marker in septic patients and patients with systemic inflammatory response syndrome (SIRS). 126 patients were included into the study. The patients were divided into four groups: 1--septic patients with positive blood cultures, 2--septic patients with negative blood cultures, 3--patients with SIRS, 4--patients without sepsis and SIRS. PCT level was measured by imunoluminometric assay (LUMItest) and immunochromatographic assay (PCT-Q). PCT level is higher in patients with sepsis than in patients with SIRS. PCT level is only slightly elevated in patients without sepsis and SIRS. The highest PCT level is found in patients with septic shock. In patients with the clinical improvement the frequency of PCT level increase is approximately twice lower than in patients who died. Measurement of PCT level on the first, second and third day of hospitalization has no prognostic value. There is no significant difference in PCT level in sepsis caused by Gram positive and Gram negative bacteria. PCT is a useful marker in diagnosis of sepsis but its role in monitoring the severity of sepsis requires more clinical studies.

Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK) Expression in Malignant Melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu

2017-01-01

Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin heavy chain binding protein (BiP/GRP78) plays an important role in the endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in various human cancers. The purpose of this study is to examine the prognostic significance of BiP/GRP78 expression in patients with malignant melanoma. A total of 133 malignant melanoma patients were analyzed, and tumor specimens were stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34. BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133), respectively. BiP/GRP78 disclosed a significant relationship with PERK expression, thickness, T factor, N factor, disease staging, cell proliferation (Ki-67) and MVD (CD34). By multivariate analysis, the high expression of BiP/GRP78 was identified as an independent prognostic factor for predicting poor survival against malignant melanoma. The increased BiP/GRP78 expression was clarified as an independent prognostic marker for predicting worse outcome. ER stress marker, BiP/GRP78 could be a powerful molecular target for the treatment of malignant melanoma.

MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

PubMed

Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

2015-03-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma

PubMed Central

Wang, Jianguo; Xie, Haiyang; Li, Jie; Cao, Jili; Zhou, Lin; Zheng, Shusen

2016-01-01

The more accurate biomarkers have long been desired for hepatocellular carcinoma (HCC). Here, we characterized global large-scale proteomics of multistep hepatocarcinogenesis in an attempt to identify novel biomarkers for HCC. Quantitative data of 37874 sequences and 3017 proteins during hepatocarcinogenesis were obtained in cohort 1 of 75 samples (5 pooled groups: normal livers, hepatitis livers, cirrhotic livers, peritumoral livers, and HCC tissues) by iTRAQ 2D LC-MS/MS. The diagnostic performance of the top six most upregulated proteins in HCC group and HSP70 as reference were subsequently validated in cohort 2 of 114 samples (hepatocarcinogenesis from normal livers to HCC) using immunohistochemistry. Of seven candidate protein markers, PARP1, GS and NDRG1 showed the optimal diagnostic performance for HCC. PARP1, as a novel marker, showed comparable diagnostic performance to that of classic markers GS and NDRG1 in HCC (AUCs = 0.872, 0.856 and 0.792, respectively). A significant higher AUC of 0.945 was achieved when three markers combined. For diagnosis of HCC, the sensitivity and specificity were 88.2% and 81.0% when at least two of the markers were positive. Similar diagnostic values of PARP1, GS and NDRG1 were confirmed by immunohistochemistry in cohort 3 of 180 HCC patients. Further analysis indicated that PARP1 and NDRG1 were associated with some clinicopathological features, and the independent prognostic factors for HCC patients. Overall, global large-scale proteomics on spectrum of multistep hepatocarcinogenesis are obtained. PARP1 is a novel promising diagnostic/prognostic marker for HCC, and the three-marker panel (PARP1, GS and NDRG1) with excellent diagnostic performance for HCC was established. PMID:26883192

Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors.

PubMed

Ahmed, Atif A; Zhang, Lei; Reddivalla, Naresh; Hetherington, Maxine

2017-04-01

Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8-10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.

Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.

PubMed

Menéndez, R; Martínez, R; Reyes, S; Mensa, J; Filella, X; Marcos, M A; Martínez, A; Esquinas, C; Ramirez, P; Torres, A

2009-07-01

Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

The prognostic value of Ki-67 expression in penile squamous cell carcinoma.

PubMed

Stankiewicz, Elzbieta; Ng, Mansum; Cuzick, Jack; Mesher, David; Watkin, Nick; Lam, Wayne; Corbishley, Cathy; Berney, Daniel M

2012-06-01

To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival. 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients. Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival. Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.

Evaluating a 4-marker signature of aggressive prostate cancer using time-dependent AUC.

PubMed

Gerke, Travis A; Martin, Neil E; Ding, Zhihu; Nuttall, Elizabeth J; Stack, Edward C; Giovannucci, Edward; Lis, Rosina T; Stampfer, Meir J; Kantoff, Phillip W; Parmigiani, Giovanni; Loda, Massimo; Mucci, Lorelei A

2015-12-01

We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n = 347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. During a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. © 2015 Wiley Periodicals, Inc.

Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

PubMed

Lester, R J G; Moore, B R

2015-01-01

Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis.

PubMed

Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-10-10

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16-1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50-4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046-1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103-1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393-7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis.

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis

PubMed Central

Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-01-01

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16–1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50–4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046–1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103–1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393–7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis. PMID:29137343

Developing genome-wide microsatellite markers of bamboo and their applications on molecular marker assisted taxonomy for accessions in the genus Phyllostachys.

PubMed

Zhao, Hansheng; Yang, Li; Peng, Zhenhua; Sun, Huayu; Yue, Xianghua; Lou, Yongfeng; Dong, Lili; Wang, Lili; Gao, Zhimin

2015-01-26

Morphology-based taxonomy via exiguously reproductive organ has severely limitation on bamboo taxonomy, mainly owing to infrequent and unpredictable flowering events of bamboo. Here, we present the first genome-wide analysis and application of microsatellites based on the genome of moso bamboo (Phyllostachys edulis) to assist bamboo taxonomy. Of identified 127,593 microsatellite repeat-motifs, the primers of 1,451 microsatellites were designed and 1,098 markers were physically mapped on the genome of moso bamboo. A total of 917 markers were successfully validated in 9 accessions with ~39.8% polymorphic potential. Retrieved from validated microsatellite markers, 23 markers were selected for polymorphic analysis among 78 accessions and 64 alleles were detected with an average of 2.78 alleles per primers. The cluster result indicated the majority of the accessions were consistent with their current taxonomic classification, confirming the suitability and effectiveness of the developed microsatellite markers. The variations of microsatellite marker in different species were confirmed by sequencing and in silico comparative genome mapping were investigated. Lastly, a bamboo microsatellites database (http://www.bamboogdb.org/ssr) was implemented to browse and search large information of bamboo microsatellites. Consequently, our results of microsatellite marker development are valuable for assisting bamboo taxonomy and investigating genomic studies in bamboo and related grass species.

A Distributed Approach to System-Level Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates.

PubMed

Honda, Shohei; Minato, Masashi; Suzuki, Hiromu; Fujiyoshi, Masato; Miyagi, Hisayuki; Haruta, Masayuki; Kaneko, Yasuhiko; Hatanaka, Kanako C; Hiyama, Eiso; Kamijo, Takehiko; Okada, Tadao; Taketomi, Akinobu

2016-06-01

Hepatoblastoma (HB) is very rare but the most common malignant neoplasm of the liver occurring in children. Despite improvements in therapy, outcomes for patients with advanced HB that is refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the survival rate among this group, identification of novel prognostic markers and therapeutic targets is needed. We have previously reported that altered DNA methylation patterns are of biological and clinical importance in HB. In the present study, using genome-wide methylation analysis and bisulfite pyrosequencing with specimens from HB tumors, we detected nine methylated genes. We then focused on four of those genes, GPR180, MST1R, OCIAD2, and PARP6, because they likely encode tumor suppressors and their increase of methylation was associated with a poor prognosis. The methylation status of the four genes was also associated with age at diagnosis, and significant association with the presence of metastatic tumors was seen in three of the four genes. Multivariate analysis revealed that the presence of metastatic tumors and increase of methylation of GPR180 were independent prognostic factors affecting event-free survival. These findings indicate that the four novel tumor suppressor candidates are potentially useful molecular markers predictive of a poor outcome in HB patients, which may serve as the basis for improved therapeutic strategies when clinical trials are carried out. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

PubMed Central

2011-01-01

Introduction Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. Methods MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Results Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Conclusions Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy. PMID:21888627

New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images

PubMed Central

Chen, Jia-Mei; Qu, Ai-Ping; Wang, Lin-Wei; Yuan, Jing-Ping; Yang, Fang; Xiang, Qing-Ming; Maskey, Ninu; Yang, Gui-Fang; Liu, Juan; Li, Yan

2015-01-01

Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001 - 1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537 - 0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177 - 2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142 - 2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors. PMID:26022540

CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

PubMed

Pilati, C; Taieb, J; Balogoun, R; Marisa, L; de Reyniès, A; Laurent-Puig, P

2017-05-01

Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer.

PubMed

Schläfli, Anna M; Adams, Olivia; Galván, José A; Gugger, Mathias; Savic, Spasenija; Bubendorf, Lukas; Schmid, Ralph A; Becker, Karl-Friedrich; Tschan, Mario P; Langer, Rupert; Berezowska, Sabina

2016-06-28

Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non-small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters.LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4).The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior.

Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer

PubMed Central

Schläfli, Anna M.; Adams, Olivia; Galván, José A.; Gugger, Mathias; Savic, Spasenija; Bubendorf, Lukas; Schmid, Ralph A.; Becker, Karl-Friedrich; Tschan, Mario P.; Langer, Rupert; Berezowska, Sabina

2016-01-01

Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non-small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters. LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4). The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior. PMID:27250032

Identification of prognostic markers in transthyretin and AL cardiac amyloidosis.

PubMed

Damy, Thibaud; Jaccard, Arnaud; Guellich, Aziz; Lavergne, David; Galat, Arnault; Deux, Jean-François; Hittinger, Luc; Dupuis, Jehan; Frenkel, Valérie; Rigaud, Charlotte; Plante-Bordeneuve, Violaine; Bodez, Diane; Mohty, Dania

2016-09-01

The prognosis of amyloidosis is known to depend heavily on cardiac function and may be improved by identifying patients at highest risk for adverse cardiac events. Identify predictors of mortality in patients with cardiac light-chain amyloidosis (AL), hereditary transthyretin amyloidosis (m-TTR), or wild-type transthyretin amyloidosis (WT-TTR) to prompt physician to refer these patients to dedicated centers. Observational study. About 266 patients referred for suspected cardiac amyloidosis (CA) in two French university centers were included. About 198 patients had CA (AL = 118, m-TTR = 57, and WT-TTR = 23). Their median (25th-75th percentile) age, NT-proBNP left ventricular ejection fraction were, respectively, 68 years (59-76), 2339 pg mL -1 (424-5974), and 60% (48-66). About 31% were in NYHA class III-IV. Interventricular septal thickness was greater in the m-TTR and WT-TTR groups than in the AL group (p < 0.0001). Median follow-up in survivor was 26 months (15-44) and 87 (44%) patients died. By multivariate analysis, independent predictors of mortality for AL amyloidosis were the following: age, cardiac output and NT-proBNP; for TTR amyloidosis was: NT-proBNP. When all amyloidosis were combined NT-proBNP, low cardiac output and pericardial effusion were independently associated with mortality. NT-proBNP is a strong prognosticator in the three types of cardiac amyloidosis. High NT-proBNP, low cardiac output, and pericardial effusion at the time of screening should prompt physician to refer the patients to amyloidosis referral center.

Generic Software Architecture for Prognostics (GSAP) User Guide

NASA Technical Reports Server (NTRS)

Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

2016-01-01

The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

Distilling the Verification Process for Prognostics Algorithms

NASA Technical Reports Server (NTRS)

Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

2013-01-01

The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2014-01-01

There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke.

PubMed

Fischer, Marlene; Katan, Mira; Morgenthaler, Nils G; Seiler, Marleen; Müller, Beat; Lackner, Peter; Errath, Mario; Helbok, Raimund; Pfausler, Bettina; Beer, Ronny; Schmutzhard, Erich; Broessner, Gregor

2014-01-01

Atrial natriuretic peptide (ANP) is a well-known prognostic marker of outcome and mortality in patients with cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP) is a stable fragment of the ANP precursor hormone. As a prognostic marker after ischemic stroke, it reliably predicts poststroke mortality and functional outcome. This study aimed to analyze the prognostic value of MR-proANP in patients with hemorrhagic stroke, i.e. subarachnoid (SAH) and intracerebral hemorrhage (ICH). MR-proANP was analyzed in patients with spontaneous SAH or spontaneous ICH. All patients were prospectively randomized into two treatment arms: (1) a prophylactic normothermia group with a target core temperature 36.5°C using endovascular cooling, and (2) a control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on admission and on days 4 and 7. Measurement of MR-proANP was performed in serum using sandwich immunoassay. The primary endpoint was functional outcome [assessed by the Glasgow Outcome Score (GOS)] and the secondary endpoints were mortality within 180 days after hemorrhagic stroke and influence of temperature on MR-proANP. A favorable outcome was defined as GOS 4-5, and the patients were considered to have a poor outcome with a 180-day GOS score between 1 and 3. Analysis of MR-proANP was performed in 24 patients with spontaneous SAH and 22 patients with spontaneous ICH. MR-proANP was elevated on days 4 and 7 as compared to baseline levels (p < 0.05 and p < 0.001, respectively). High MR-proANP levels (>120 pmol/l) were associated with increased mortality and poor outcome (after 180 days; p < 0.05, respectively). There was no significant difference regarding MR-proANP serum concentrations between the endovascular and the control groups. Increased levels of MR-proANP are independently associated with poor functional outcome and increased mortality after 180 days in

Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma.

PubMed

Liu, Jian-Dong; Xin, Qun; Tao, Chun-Sheng; Sun, Pei-Feng; Xu, Peng; Wu, Bing; Qu, Liang; Li, Shu-Zhong

2016-11-01

In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR-300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma.

Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma

PubMed Central

Liu, Jian-Dong; Xin, Qun; Tao, Chun-Sheng; Sun, Pei-Feng; Xu, Peng; Wu, Bing; Qu, Liang; Li, Shu-Zhong

2016-01-01

In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR-300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma. PMID:27895748

A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

PubMed Central

Pan, Qun-Xiong; Su, Zi-Jian; Zhang, Jian-Hua; Wang, Chong-Ren; Ke, Shao-Ying

2015-01-01

Background People’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors. Objective To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM) stage in patients undergoing gastric cancer resection. Methods The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and prognostic index (PI) were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage. Results In univariate analysis, preoperative serum C-reactive protein (P<0.001), serum albumin (P<0.001), GPS (P<0.001), PLR (P=0.002), NLR (P<0.001), PI (P<0.001), PNI (P<0.001), and TNM stage (P<0.001) were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024), NLR (P=0.012), PI (P=0.001), TNM stage (P<0.001), and degree of differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating

Evaluating biomarkers for prognostic enrichment of clinical trials.

PubMed

Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

PubMed

Abdulmajed, Mohamed Ismat; Sancak, Eyüp Burak; Reşorlu, Berkan; Al-Chalaby, Gydhia Zuhair

2014-12-01

Urothelial carcinoma is the 9(th) most common cancer worldwide. Most urothelial tumors are non-muscle invasive on presentation. However, two-thirds of non-invasive bladder cancers will eventually recur with a 25% risk of progression to muscle-invasive bladder cancer. Tumor stage, histological grade and pathological invasion of blood vessels and lymphatic tissue are the main indicators for urothelial cancer prognosis. The gold standard for diagnosing bladder cancer is conventional white-light cystoscopy and biopsy. Urine cytology is a highly specific, sensitive test for high-grade tumors or carcinoma in situ (CIS). Urinary NMP22 has an overall sensitivity and specificity for detecting bladder cancer of 49% and 87%, respectively. However, there are false-positive results in the presence of urinary tract infection or hematuria. The detection of specific gene mutations related to urothelial cancers has been studied and employed to reproduce markers helpful for diagnosis. According to current studies, molecular markers can be used to predict tumor recurrence. From a prognostic point of view, new molecular markers have yet to be established as reliable indicators of tumor aggressiveness. We aimed to review the molecular markers with possible prognostic significance that have been discussed in the literature. This review examined the literature for various molecular markers under development for bladder cancer in an attempt to optimize patient care and reduce the costs of treating these patients.

Snakebite mediated acute kidney injury, prognostic predictors, oxidative and carbonyl stress: A prospective study.

PubMed

Mukhopadhyay, P; Mishra, R; Mukherjee, D; Mishra, R; Kar, M

2016-01-01

Snake bite is an occupational hazard in India and important preventable cause of acute kidney injury (AKI). This study was done to estimate the magnitude of snakebite-induced AKI (SAKI) who required renal replacement therapy, prognostic predictors, and final outcome, and to measure the oxidative and carbonyl stress (CS) level in SAKI patient who underwent hemodialysis (HD). All SAKI patients dialyzed between April 2010 and July 2011 in NRS Medical College were included. Demographical, clinical, and biochemical data were analyzed, and patients are followed to discharge or death. Oxidative and CS markers (advanced oxidation protein product [AOPP], advanced glycation end product, pentosidine, dityrosine, thioberbituric acid reactive substance, and methylglyoxal [MG]) were measured in 48 SAKI patient requiring HD. About 155 SAKI patients (M: F 2.2:1) received HD. Of them. The age was 36.2 (range 4-74) years. The most common site of the bite was lower limb (88.7%). Oliguria and bleeding manifestation were the common presentation. Hypotension was found in 52 (33.5%) cases, cellulitis and inflammation were found in about 63%. Mean creatinine was 4.56 ± 0.24 mg/dl. About 42 (27.1%) had disseminated intravascular coagulation (DIC). 36 (78.2%) had cellulites, 24 (52.2%) had hypotension or shock at initial presentation ( P < 0.05), bleeding manifestation was found in 37 (80.4%), and 22 (47.8%) had DIC ( P < 0.05). Forty-six (29.7%) patient died. DIC and hypotension/shock at initial presentation came out as an independent predictor of death. Among all markers measured for oxidative and CS ( n = 48) AOPP and MG came out as an independent predictor ( P < 0.05) of adverse outcome. Hypotension, DIC, AOPP, and MG were a poor prognostic marker in SAKI patients requiring dialysis.

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

PubMed Central

Choi, Ji Soo; Baek, Hyeon-Man; Kim, Suhkmann; Kim, Min Jung; Youk, Ji Hyun; Moon, Hee Jung; Kim, Eun-Kyung; Han, Kyung Hwa; Kim, Dong-hyun; Kim, Seung Il; Koo, Ja Seung

2012-01-01

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization. PMID:23272149

Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

PubMed

Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-07

Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

The Promise of Novel Molecular Markers in Bladder Cancer

PubMed Central

Miremami, Jahan; Kyprianou, Natasha

2014-01-01

Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

PubMed

Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

2016-06-01

This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study.

PubMed

Giussani, G; Canelli, V; Bianchi, E; Erba, G; Franchi, C; Nobili, A; Sander, J W; Beghi, E

2016-07-01

Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs. © 2016 EAN.

Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: a prospective study.

PubMed

Dwivedi, Shailendra; Goel, Apul; Natu, Shanker M; Mandhani, Anil; Khattri, Sanjay; Pant, Kamlesh K

2011-01-01

specificity and sensitivity and IL-10 may be valuable as a prognostic marker than PSA in carcinoma prostate.

The Glasgow Prognostic Score as a significant predictor of diffuse large B cell lymphoma treated with R-CHOP in China.

PubMed

Li, Xiaoyang; Zhang, Yunxiang; Zhao, Weili; Liu, Zhao; Shen, Yang; Li, Junmin; Shen, Zhixiang

2015-01-01

The Glasgow Prognostic Score (GPS) incorporates C-reactive protein and albumin as clinically useful markers of tumor behavior and shows significant prognostic value in several types of solid tumors. The accuracy of the GPS in predicting outcomes in diffuse large B cell lymphoma (DLBCL) remains unknown. We performed this study to evaluate the prognostic significance of the GPS in DLBCL in China. We retrospectively analyzed 160 patients with newly diagnosed DLBCL at the Shanghai Ruijin Hospital (China). The prognostic value of the GPS was evaluated and compared with that of the International Prognostic Index (IPI) and immunohistochemical subtyping. The GPS was defined as follows: GPS-0, C-reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L; GPS-1, CRP >10 mg/L or albumin <35 g/L; and GPS-2, CRP >10 mg/L and albumin <35 g/L. Patients with lower GPS tended to have better outcomes including progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS and high IPI score were independent adverse predictors of OS. Similar to several other tumors, GPS is a reliable predictor of survival outcomes in DLBCL patients treated with R-CHOP therapy. Inflammatory responses are implicated in the progression and survival of patients with DLBCL.

Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

PubMed

Ryan, Deborah; Carberry, Steven; Murphy, Áine C; Lindner, Andreas U; Fay, Joanna; Hector, Suzanne; McCawley, Niamh; Bacon, Orna; Concannon, Caoimhin G; Kay, Elaine W; McNamara, Deborah A; Prehn, Jochen H M

2016-07-01

Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

beta(2)microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients.

PubMed

Shrout, J; Yousefzadeh, M; Dodd, A; Kirven, K; Blum, C; Graham, A; Benjamin, K; Hoda, R; Krishna, M; Romano, M; Wallace, M; Garrett-Mayer, E; Mitas, M

2008-06-17

Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT-PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I-IV CRC patients with (n=20) and without (n=18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of beta(2)microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69-0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC=0.87; 95% CI=0.71-0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R(2) value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival.

Tumour-marker levels and prognosis in malignant teratoma of the testis.

PubMed Central

Germa-Lluch, J. R.; Begent, R. H.; Bagshawe, K. D.

1980-01-01

The effect of 6 putative prognostic factors on survival was studied in patients with Stages III and IV malignant teratoma of the testis. Differences between survival curves were tested for statistical significance. A diameter greater than 5 cm in the largest tumour mass, and greater than 8 pulmonary metastases were adverse prognostic factors (P = 0.004 and 0.008 respectively). Patients with malignant teratoma, trophoblastic, fared worse than those with malignant teratoma, undifferentiated, and malignant teratoma, intermediate (P = 0.011 and 0.023 respectively). Previous chemotherapy or radiotherapy had no significant effect. Serum alpha-foetoprotein (AFP) above 10(3) MRC u/ml and serum beta subunit of human chorionic gonadotrophin (hCG) above 10(5) miu/ml, were found to predict a poor prognosis (P = 0.010 and 0.001 respectively). A combination of measurements of the tumour markers gave the most consistent indication of prognosis, in that patients with either AFP greater than 10(3) MRC u/ml or hCG greater than 10(5) miu/ml, or both, fared much worse than those with neither factor (P = 0.001). Serum concentrations of AFP and hCG should be stated in reports of treatment of testicular teratoma in order to provide a basis for comparison with other series. Regular and frequent measurements of these markers are appropriate throughout the clinical management of patients with malignant teratoma. PMID:6161630

Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

PubMed

Arenja, Nisha; Riffel, Johannes H; Fritz, Thomas; André, Florian; Aus dem Siepen, Fabian; Mueller-Hennessen, Matthias; Giannitsis, Evangelos; Katus, Hugo A; Friedrich, Matthias G; Buss, Sebastian J

2017-06-01

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental

Aberrant expression of cancer stem cell markers (CD44, CD90, and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients: 4-year survival data.

PubMed

Bahnassy, Abeer A; Fawzy, Mohamed; El-Wakil, Mohamed; Zekri, Abdel-Rahman N; Abdel-Sayed, Ahmed; Sheta, Marwa

2015-03-01

Hepatoblastoma (HB) is an embryonal tumor of the liver in children. Prognosis and response to treatment in HB are highly variable. Cancer stem cells (CSCs) constitute a population of cells, which contribute to the development and progression of many tumors. However, their role in HB is not well defined yet. We assessed the prognostic and predictive values of some CSC markers in HB patients. Protein and messenger RNA expressions of the CSC markers CD133, CD90, and CD44 were assessed in 43 HB patients and 20 normal hepatic tissues using immunohistochemistry and quantitative real-time polymerase chain reaction. The expression levels of these markers were correlated to standard prognostic factors, patients' response to treatment, overall survival (OS), and disease-free survival (DFS). CD44, CD90, and CD133 proteins were detected in 48.8%, 32.6%, and 48.8% compared with 46.5%, 41.7%, and 58.1% RNA, respectively (concordance, 77.8%-96%). None of the normal tissue samples was positive for any of the markers. Significant correlations were reported between α-fetoprotein and both CD44 and CD133 (P = 0.02) as well as between tumor types CD90 and CD133 (P = 0.009). Reduced OS correlated with CD44, CD90, and CD133 expressions (P < 0.001), advanced stage (P < 0.001), response to treatment (P < 0.001), and total excision of the tumor. Reduced DFS correlated with CD44 and CD133 expressions (P < 0.001) only. In conclusion, CD133, CD44, and CD90 could be used as prognostic and predictive markers in HB. High expression of these markers is significantly associated with poor response to treatment and reduced survival. Moreover, complete surgical resection and systemic chemotherapy are essential to achieve good response and prolonged survival, especially in early stage patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Fragmented QRS complex is a prognostic marker of microvascular reperfusion and changes in LV function occur in patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

PubMed

Zhang, Ruoxi; Chen, Shuyuan; Zhao, Qi; Sun, Meng; Yu, Bo; Hou, Jingbo

2017-06-01

The present study aimed to investigate the in-hospital and long-term prognostic value of fragmented QRS complex (fQRS) for microvascular reperfusion and changes in left ventricular (LV) function in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). A total of 216 patients with STEMI undergoing primary PCI were included in the current study. Patients were divided into two groups based on the presence (n=126) or absence (n=90) of fQRS following electrocardiograms (ECGs) on admission. Following primary PCI and follow up, patients were divided into four groups based on new onset, resolution, persistence and absence of fQRS. Major adverse cardiac events were defined to include cardiovascular death, arrhythmia, heart failure, reinfarction and target vessel revascularization. The percentage of patients with heart failure and microvascular reperfusion differed significantly between the fQRS(+) and fQRS(-) groups. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), Peak creatine kinase-MB (CK-MB) and Troponin I levels were observed to be significantly higher in the fQRS(+) group compared with the fQRS(-) group. In univariate logistic regression analysis, left ventricular ejection fraction (LVEF), NT-proBNP, Troponin I, Peak CK-MB and microvascular reperfusion were found to be associated with fQRS. Multivariate analysis identified that LVEF, NT-proBNP, Troponin I and microvascular reperfusion may be independent predictors of fQRS. The presence of fQRS was demonstrated to be associated with left ventricular dysfunction at follow up assessments. The presence of fQRS was not only significantly associated with myocardial microvascular reperfusion and left ventricular function, but was also a prognostic marker in STEMI.

Model-Based Prognostics of Hybrid Systems

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

2015-01-01

Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

Distributed Prognostic Health Management with Gaussian Process Regression

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

2010-01-01

Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

PubMed

Mayoral, M; Fernandez-Martinez, A; Vidal, L; Fuster, D; Aya, F; Pavia, J; Pons, F; Lomeña, F; Paredes, P

2016-01-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma.

PubMed

Yang, Xinan Holly; Tang, Fangming; Shin, Jisu; Cunningham, John M

2017-10-03

Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children. We systematically assembled genomic variants, gene expression changes, priori knowledge of gene functions, and clinical outcomes to identify prognostic multigene signatures. First, we assigned a new, individualized prognostic index using the relative expressions between the poor- and good-outcome signature genes. We then characterized HR-NB aggressiveness beyond these prognostic multigene signatures through the imbalanced effects of MYC and PRC2 signaling. We further analyzed Retinoic acid (RA)-induced HR-NB cells to model tumor cell differentiation. Finally, we performed in vitro validation on ZFHX3, a cell differentiation marker silenced by PRC2, and compared cell morphology changes before and after blocking PRC2 in HR-NB cells. A significant concurrence existed between exons with verified variants and genes showing MYCN-dependent expression in HR-NB. From these biomarker candidates, we identified two novel prognostic gene-set pairs with multi-scale oncogenic defects. Intriguingly, MYC targets over-represented an unfavorable component of the identified prognostic signatures while PRC2 targets over-represented a favorable component. The cell cycle arrest and neuronal differentiation marker ZFHX3 was identified as one of PRC2-silenced tumor suppressor candidates. Blocking PRC2 reduced tumor cell growth and increased the mRNA expression levels of ZFHX3 in an early treatment stage. This hypothesis-driven systems bioinformatics work offered novel insights into

Supportive Care: Time to Change Our Prognostic Tools and Their Use in CKD

PubMed Central

Hemmelgarn, Brenda; Kotanko, Peter; Germain, Michael J.; Moranne, Olivier; Davison, Sara N.

2016-01-01

In using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist’s recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients’ values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients’ priorities in development of new scores. Delivering patient-centered care requires an understanding of patients’ priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients’ health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health–related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient–centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely

Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

PubMed

Tam, Frederick W K; Riser, Bruce L; Meeran, Karim; Rambow, JoAnn; Pusey, Charles D; Frankel, Andrew H

2009-07-01

Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.

Early pregnancy factor as a marker for assessing embryonic viability in threatened and missed abortions.

PubMed

Shahani, S K; Moniz, C L; Bordekar, A D; Gupta, S M; Naik, K

1994-01-01

It is now well recognized that the presence of early pregnancy factor (EPF) can signify the occurrence of fertilization, continuation of pregnancy and the existence of a viable embryo. With this in view, a study was undertaken to observe the potential of EPF as a marker in assessing embryo viability in cases complicated with vaginal bleeding during early pregnancy. The results indicated that the sensitivity of EPF as a marker in predicting threatened or missed abortion was 78.9% and the specificity 95.6%. The positive predictive value was observed to be 93.8% and the negative predictive value 84.6%. Our studies have shown that since EPF is present in viable but absent in non-viable pregnancies, it could be a useful marker of prognostic value in threatened abortions.

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer

PubMed Central

Garcia, J M; Rodriguez, R; Dominguez, G; Silva, J M; Provencio, M; Silva, J; Colmenarejo, A; Millan, I; Muñoz, C; Salas, C; Coca, S; España, P; Bonilla, F

2003-01-01

Background: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. Aims: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. Patients and methods: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. Results: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p = 0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p = 0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p = 0.02). Multivariate analysis in the complete series showed that stage (p = 0.006) and lymph node metastases (⩾4 nodes, p = 0.0001; 1–3 nodes, p = 0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p = 0.001). Conclusions: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II. PMID:14633957

Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

PubMed

Papagiorgis, Petros Christakis

2016-05-01

Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

Valuable water

NASA Astrophysics Data System (ADS)

Carlowicz, Michael

In some places, money flows with water. Studying both the water quality and property values around 22 lakes in south-central Maine, Kevin Boyle and Holly James of the University of Maine and Roy Bouchard of the Maine Department of Environmental Protection have found that good water quality makes waterfront property even more valuable. To gauge water quality, the researchers used Secchi disks to measure the clarity of the water at depth. They also reviewed 543 lakefront property sales between 1990 and 1994 to determine how values correlated with changing water conditions. The group also considered such factors as lake frontage, sizes of the houses and lots, and size of the lake.

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

PubMed

Porcaro, Antonio B; Monaco, Carmelo; Romano, Mario; Petrozziello, Aldo; Rubilotta, Emanuele; Lacola, Vincenzo; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Antoniolli, Stefano Zecchini; Migliorini, Filippo; Comunale, Luigi

2010-01-01

To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) μg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and p

Prognostic value of circulating tumor cells in esophageal cancer.

PubMed

Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

2017-02-21

To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted.

Cthrc1 overexpression is an independent prognostic marker in gastric cancer.

PubMed

Gu, Lina; Liu, Lei; Zhong, Lili; Bai, Yuxian; Sui, Hong; Wei, Xiaoli; Zhang, Wenjie; Huang, Peng; Gao, Dandan; Kong, Ying; Lou, Ge

2014-05-01

Collagen triple helix repeat containing 1 (CTHRC1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury and was found to be overexpressed in several malignant tumors, such as breast cancer and malignant melanoma. However, the expression of Cthrc1 and its role in gastric cancer progression remain unknown. We investigated the expression of the Cthrc1 protein by immunohistochemistry in 30 normal tissues from the control subjects and 166 gastric carcinomas and analyzed its correlation with various clinicopathological features, including patient outcome. Cthrc1 immunoreactivity was overexpressed in gastric carcinoma cases compared with normal tissues (P < .001). High Cthrc1 expression was found in 108 (65.06%) of these 166 carcinomas and was positively correlated with the American Joint Committee on Cancer stage classification, depth of gastric wall invasion, lymph node metastasis, lymphovascular space involvement, and recurrence but not with age, tumor site, and carcinoembryonic antigen level. Patients with high Cthrc1 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of Cthrc1 (P = .001 and P = .002, respectively). Multivariate analysis showed that high Cthrc1 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with gastric carcinoma (both P = .005). These results showed that high Cthrc1 expression was associated with progression and prognosis of gastric carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

PubMed

Fizazi, Karim; Culine, Stéphane; Kramar, Andrew; Amato, Robert J; Bouzy, Jeannine; Chen, Isan; Droz, Jean-Pierre; Logothetis, Christopher J

2004-10-01

The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

Prognostic stratification of gliomatosis cerebri by IDH1 R132H and INA expression.

PubMed

Desestret, Virginie; Ciccarino, Pietro; Ducray, François; Crinière, Emmanuelle; Boisselier, Blandine; Labussière, Marianne; Polivka, Marc; Idbaih, Ahmed; Kaloshi, Gentian; von Deimling, Andreas; Hoang-Xuan, Khe; Delattre, Jean-Yves; Mokhtari, Karima; Sanson, Marc

2011-11-01

Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.

Glasgow Coma Scale and Its Components on Admission: Are They Valuable Prognostic Tools in Acute Mixed Drug Poisoning?

PubMed Central

Eizadi Mood, N.; Sabzghabaee, A. M.; Yadegarfar, Gh.; Yaraghi, A.; Ramazani Chaleshtori, M.

2011-01-01

Introduction. The verbal, eye, and motor components of Glasgow coma scale (GCS) may be influenced by poisoned patients' behavior in an attempted suicide. So, the values of admission GCS and its components for outcomes prediction in mixed drugs poisoning were investigated. Materials and Methods. A followup study data was performed on patients with mixed drugs poisoning. Outcomes were recorded as without complications and with complications. Discrimination was evaluated by calculating the area under the receiver operating characteristic curves (AUC). Results. There was a significant difference between the mean value of each component of GCS as well as the total GCS between patients with and without complication. Discrimination was best for GCS (AUC: 0.933 ± 0.020) and verbal (0.932 ± 0.021), followed by motor (0.911 ± 0.025), then eye (0.89 ± 0.028). Conclusions. Admission GCS and its components seem to be valuable in outcome prediction of patients with mixed drug poisoning. PMID:21559299

Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis

PubMed Central

Meher, Susanta; Mishra, Tushar Subhadarshan; Sasmal, Prakash Kumar; Rath, Satyajit; Sharma, Rakesh; Rout, Bikram; Sahu, Manoj Kumar

2015-01-01

Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis. PMID:26345247

Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects

PubMed Central

Neubauer, Elisa; Wirtz, Ralph M.; Kaemmerer, Daniel; Athelogou, Maria; Schmidt, Lydia; Sänger, Jörg; Lupp, Amelie

2016-01-01

The classification of bronchopulmonary neuroendocrine neoplasms (BP-NEN) into four tumor entities (typical carcinoids (TC), atypical carcinoids (AC), small cell lung cancers (SCLC), large cell neuroendocrine lung carcinomas (LCNEC)) is difficult to perform accurately, but important for prognostic statements and therapeutic management decisions. In this regard, we compared the expression of three proliferation markers, Ki-67, Topoisomerase II alpha (TOP2A), and RacGAP1, in a series of tumor samples from 104 BP-NEN patients (24 TC, 21 AC, 52 SCLC, 7 LCNEC) using different evaluation methods (immunohistochemistry (IHC): Average evaluation, Hotspot evaluation, digital image analysis; RT-qPCR). The results indicated that all three markers had increased protein and mRNA expression with poorer differentiation and correlated well with each other, as well as with grading, staging, and poor survival. Compared with Ki-67 and TOP2A, RacGAP1 allowed for a clearer prognostic statement. The cut-off limits obtained for Ki-67-Average (IHC) were TC-AC 1.5, AC-SCLC 19, and AC-LCNEC 23.5. The Hotspot evaluation generated equal to higher, the digital image analysis generally lower between-entity cut-off limits. All three markers enabled a clear-cut differentiation between the BP-NEN entities, and all methods evaluated were suitable for marker assessment. However, to define optimal cut-off limits, the Ki-67 evaluation methods should be standardized. RacGAP1 appeared to be a new marker with great potential. PMID:27259241

Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects.

PubMed

Neubauer, Elisa; Wirtz, Ralph M; Kaemmerer, Daniel; Athelogou, Maria; Schmidt, Lydia; Sänger, Jörg; Lupp, Amelie

2016-07-05

The classification of bronchopulmonary neuroendocrine neoplasms (BP-NEN) into four tumor entities (typical carcinoids (TC), atypical carcinoids (AC), small cell lung cancers (SCLC), large cell neuroendocrine lung carcinomas (LCNEC)) is difficult to perform accurately, but important for prognostic statements and therapeutic management decisions. In this regard, we compared the expression of three proliferation markers, Ki-67, Topoisomerase II alpha (TOP2A), and RacGAP1, in a series of tumor samples from 104 BP-NEN patients (24 TC, 21 AC, 52 SCLC, 7 LCNEC) using different evaluation methods (immunohistochemistry (IHC): Average evaluation, Hotspot evaluation, digital image analysis; RT-qPCR).The results indicated that all three markers had increased protein and mRNA expression with poorer differentiation and correlated well with each other, as well as with grading, staging, and poor survival. Compared with Ki-67 and TOP2A, RacGAP1 allowed for a clearer prognostic statement. The cut-off limits obtained for Ki-67-Average (IHC) were TC-AC 1.5, AC-SCLC 19, and AC-LCNEC 23.5. The Hotspot evaluation generated equal to higher, the digital image analysis generally lower between-entity cut-off limits.All three markers enabled a clear-cut differentiation between the BP-NEN entities, and all methods evaluated were suitable for marker assessment. However, to define optimal cut-off limits, the Ki-67 evaluation methods should be standardized. RacGAP1 appeared to be a new marker with great potential.

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors.

PubMed

Karaoğlu, Aziz; Yalcin, Suayib; Tekuzman, Gülten; Kars, Ayse; Celik, Ismail; Güler, Nilüfer; Ozişik, Yavuz; Türker, Alev; Barişta, Ibrahim; Güllü, Ibrahim

2003-01-01

We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Expression of Vascular Notch Ligand Delta-Like 4 and Inflammatory Markers in Breast Cancer

PubMed Central

Jubb, Adrian M.; Soilleux, Elizabeth J.; Turley, Helen; Steers, Graham; Parker, Andrew; Low, Irene; Blades, Jennifer; Li, Ji-Liang; Allen, Paul; Leek, Russell; Noguera-Troise, Irene; Gatter, Kevin C.; Thurston, Gavin; Harris, Adrian L.

2010-01-01

Delta-like ligand 4 (Dll4) is a Notch ligand that is predominantly expressed in the endothelium. Evidence from xenografts suggests that inhibiting Dll4 may overcome resistance to antivascular endothelial growth factor therapy. The aims of this study were to characterize the expression of Dll4 in breast cancer and assess whether it is associated with inflammatory markers and prognosis. We examined 296 breast adenocarcinomas and 38 ductal carcinoma in situ tissues that were represented in tissue microarrays. Additional whole sections representing 10 breast adenocarcinomas, 10 normal breast tissues, and 16 angiosarcomas were included. Immunohistochemistry was then performed by using validated antibodies against Dll4, CD68, CD14, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN), CD123, neutrophil elastase, CD31, and carbonic anhydrase 9. Dll4 was selectively expressed by intratumoral endothelial cells in 73% to 100% of breast adenocarcinomas, 18% of in situ ductal carcinomas, and all lactating breast cases, but not normal nonlactating breast. High intensity of endothelial Dll4 expression was a statistically significant adverse prognostic factor in univariate (P = 0.002 and P = 0.01) and multivariate analyses (P = 0.03 and P = 0.04) of overall survival and relapse-free survival, respectively. Among the inflammatory markers, only CD68 and DC-SIGN were significant prognostic factors in univariate (but not multivariate) analyses of overall survival (P = 0.01 and 0.002, respectively). In summary, Dll4 was expressed by endothelium associated with breast cancer cells. In these retrospective subset analyses, endothelial Dll4 expression was a statistically significant multivariate prognostic factor. PMID:20167860

Educating Tomorrow's Valuable Citizen.

ERIC Educational Resources Information Center

Burstyn, Joan N., Ed.

This collection of essays by various authors discusses the dilemmas that face those who would educate tomorrow's valuable citizens and describes the day-to-day commitment needed to maintain a community. The book gives guidelines for action through examples of current programs that provide a forum for civic discussion and public consensus on the…

Hemodynamic exercise testing. A valuable tool in the selection of cardiac transplantation candidates.

PubMed

Chomsky, D B; Lang, C C; Rayos, G H; Shyr, Y; Yeoh, T K; Pierson, R N; Davis, S F; Wilson, J R

1996-12-15

Peak exercise oxygen consumption (Vo2), a noninvasive index of peak exercise cardiac output (CO), is widely used to select candidates for heart transplantation. However, peak exercise Vo2 can be influenced by noncardiac factors such as deconditioning, motivation, or body composition and may yield misleading prognostic information. Direct measurement of the CO response to exercise may avoid this problem and more accurately predict prognosis. Hemodynamic and ventilatory responses to maximal treadmill exercise were measured in 185 ambulatory patients with chronic heart failure who had been referred for cardiac transplantation (mean left ventricular ejection fraction, 22 +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was normal in 83 patients and reduced in 102. By univariate analysis, patients with normal CO responses had a better 1-year survival rate (95%) than did those with reduced CO responses (72%) (P < .0001). Survival in patients with peak Vo2 of > 14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of < or = 14 mL.min-1.kg-1 (79%) (P = NS). However, survival was worse in patients with peak Vo2 of < or = 10 mL.min-1.kg-1 (52%) versus those with peak Vo2 of > 10 mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response was the strongest independent predictor of survival (risk ratio, 4.3), with peak Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other independent predictor. Patients with reduced CO responses and peak Vo2 of < or = 10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%). Both CO response to exercise and peak exercise Vo2 provide valuable independent prognostic information in ambulatory patients with heart failure. These variables should be used in combination to select potential heart transplantation candidates.

Rough Set Theory based prognostication of life expectancy for terminally ill patients.

PubMed

Gil-Herrera, Eleazar; Yalcin, Ali; Tsalatsanis, Athanasios; Barnes, Laura E; Djulbegovic, Benjamin

2011-01-01

We present a novel knowledge discovery methodology that relies on Rough Set Theory to predict the life expectancy of terminally ill patients in an effort to improve the hospice referral process. Life expectancy prognostication is particularly valuable for terminally ill patients since it enables them and their families to initiate end-of-life discussions and choose the most desired management strategy for the remainder of their lives. We utilize retrospective data from 9105 patients to demonstrate the design and implementation details of a series of classifiers developed to identify potential hospice candidates. Preliminary results confirm the efficacy of the proposed methodology. We envision our work as a part of a comprehensive decision support system designed to assist terminally ill patients in making end-of-life care decisions.

State of the art and taxonomy of prognostics approaches, trends of prognostics applications and open issues towards maturity at different technology readiness levels

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2017-09-01

Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.

Inflammatory markers in SIRS, sepsis and septic shock.

PubMed

Herzum, I; Renz, H

2008-01-01

Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

A novel protein-based prognostic signature improves risk stratification to guide clinical management in early lung adenocarcinoma patients.

PubMed

Martínez-Terroba, Elena; Behrens, Carmen; de Miguel, Fernando J; Agorreta, Jackeline; Monsó, Eduard; Millares, Laura; Sainz, Cristina; Mesa-Guzman, Miguel; Pérez-Gracia, Jose Luis; Lozano, María Dolores; Zulueta, Javier J; Pio, Ruben; Wistuba, Ignacio I; Montuenga, Luis M; Pajares, María J

2018-05-13

Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer patients are classified conceals hidden biological heterogeneity, manifested in heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers to assess individual patient risk is an unmet medical need. Here we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI and SLC2A1) to stratify early lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8 th edition, 2018). A test cohort (n=239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression following stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). The model resulted in a highly significant predictor of five-year outcome for disease-free survival (P<0.001) and overall survival (P<0.001). The prognostic ability of the model was externally validated in an independent multi-institutional cohort of patients (n=114, P=0.021). We also demonstrated that this molecular classifier adds relevant information to the gold standard TNM-based pathological staging with a highly significant improvement of likelihood ratio. We subsequently developed a combined prognostic index (CPI) including both the molecular and the pathological data which improved the risk stratification in both cohorts (P≤0.001). Moreover, the signature may help to select stage I-IIA patients who might benefit from adjuvant chemotherapy. In summary, this protein-based signature accurately identifies those patients with high risk of recurrence and death, and adds further prognostic information to the TNM-based clinical staging, even applying the

On Applying the Prognostic Performance Metrics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

Comparison of the Prognostic Utility of the Diverse Molecular Data among lncRNA, DNA Methylation, microRNA, and mRNA across Five Human Cancers

PubMed Central

Xu, Li; Fengji, Liang; Changning, Liu; Liangcai, Zhang; Yinghui, Li; Yu, Li; Shanguang, Chen; Jianghui, Xiong

2015-01-01

Introduction Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored. Materials and Methods We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome. Results Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71–0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables. Conclusion Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies. PMID:26606135

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy.

PubMed

Langsenlehner, Tanja; Pichler, Martin; Thurner, Eva-Maria; Krenn-Pilko, Sabine; Stojakovic, Tatjana; Gerger, Armin; Langsenlehner, Uwe

2015-05-01

Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrated multigene expression panel to prognosticate patients with gastric cancer.

PubMed

Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-04-10

Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506-0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents ( MAGED2, SYT8, BTG1 , and FAM46 ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1-3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.

Prognostic biomarkers in osteoarthritis

PubMed Central

Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

2013-01-01

Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma.

PubMed

Henderson, Samuel A; Tetzlaff, Michael T; Pattanaprichakul, Penvadee; Fox, Patricia; Torres-Cabala, Carlos A; Bassett, Roland L; Prieto, Victor G; Richards, Hunter W; Curry, Jonathan L

2014-11-01

High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC. Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival. H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035; HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT. Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review.

PubMed

Luo, Zhuang; Wu, Rong-Rong; Lv, Liang; Li, Peng; Zhang, Li-Yan; Hao, Qing-Lin; Li, Wei

2014-01-01

CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with

Recent trends and perspectives of molecular markers against fungal diseases in wheat

PubMed Central

Goutam, Umesh; Kukreja, Sarvjeet; Yadav, Rakesh; Salaria, Neha; Thakur, Kajal; Goyal, Aakash K.

2015-01-01

Wheat accounts for 19% of the total production of major cereal crops in the world. In view of ever increasing population and demand for global food production, there is an imperative need of 40–60% increase in wheat production to meet the requirement of developing world in coming 40 years. However, both biotic and abiotic stresses are major hurdles for attaining the goal. Among the most important diseases in wheat, fungal diseases pose serious threat for widening the gap between actual and attainable yield. Fungal disease management, mainly, depends on the pathogen detection, genetic and pathological variability in population, development of resistant cultivars and deployment of effective resistant genes in different epidemiological regions. Wheat protection and breeding of resistant cultivars using conventional methods are time-consuming, intricate and slow processes. Molecular markers offer an excellent alternative in development of improved disease resistant cultivars that would lead to increase in crop yield. They are employed for tagging the important disease resistance genes and provide valuable assistance in increasing selection efficiency for valuable traits via marker assisted selection (MAS). Plant breeding strategies with known molecular markers for resistance and functional genomics enable a breeder for developing resistant cultivars of wheat against different fungal diseases. PMID:26379639

Recent trends and perspectives of molecular markers against fungal diseases in wheat.

PubMed

Goutam, Umesh; Kukreja, Sarvjeet; Yadav, Rakesh; Salaria, Neha; Thakur, Kajal; Goyal, Aakash K

2015-01-01

Wheat accounts for 19% of the total production of major cereal crops in the world. In view of ever increasing population and demand for global food production, there is an imperative need of 40-60% increase in wheat production to meet the requirement of developing world in coming 40 years. However, both biotic and abiotic stresses are major hurdles for attaining the goal. Among the most important diseases in wheat, fungal diseases pose serious threat for widening the gap between actual and attainable yield. Fungal disease management, mainly, depends on the pathogen detection, genetic and pathological variability in population, development of resistant cultivars and deployment of effective resistant genes in different epidemiological regions. Wheat protection and breeding of resistant cultivars using conventional methods are time-consuming, intricate and slow processes. Molecular markers offer an excellent alternative in development of improved disease resistant cultivars that would lead to increase in crop yield. They are employed for tagging the important disease resistance genes and provide valuable assistance in increasing selection efficiency for valuable traits via marker assisted selection (MAS). Plant breeding strategies with known molecular markers for resistance and functional genomics enable a breeder for developing resistant cultivars of wheat against different fungal diseases.

Oral cancer prognosis based on clinicopathologic and genomic markers using a hybrid of feature selection and machine learning methods

PubMed Central

2013-01-01

Background Machine learning techniques are becoming useful as an alternative approach to conventional medical diagnosis or prognosis as they are good for handling noisy and incomplete data, and significant results can be attained despite a small sample size. Traditionally, clinicians make prognostic decisions based on clinicopathologic markers. However, it is not easy for the most skilful clinician to come out with an accurate prognosis by using these markers alone. Thus, there is a need to use genomic markers to improve the accuracy of prognosis. The main aim of this research is to apply a hybrid of feature selection and machine learning methods in oral cancer prognosis based on the parameters of the correlation of clinicopathologic and genomic markers. Results In the first stage of this research, five feature selection methods have been proposed and experimented on the oral cancer prognosis dataset. In the second stage, the model with the features selected from each feature selection methods are tested on the proposed classifiers. Four types of classifiers are chosen; these are namely, ANFIS, artificial neural network, support vector machine and logistic regression. A k-fold cross-validation is implemented on all types of classifiers due to the small sample size. The hybrid model of ReliefF-GA-ANFIS with 3-input features of drink, invasion and p63 achieved the best accuracy (accuracy = 93.81%; AUC = 0.90) for the oral cancer prognosis. Conclusions The results revealed that the prognosis is superior with the presence of both clinicopathologic and genomic markers. The selected features can be investigated further to validate the potential of becoming as significant prognostic signature in the oral cancer studies. PMID:23725313

The prognostic value of individual NT-proBNP values in chronic heart failure does not change with advancing age.

PubMed

Frankenstein, L; Clark, A L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Grabs, F; Nelles, M; Cleland, J G F; Katus, H A; Zugck, C

2009-05-01

It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes. To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF). Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443). University hospital outpatient departments in the UK and Germany. Chronic stable heart failure due to systolic left ventricular dysfunction. None. All-cause mortality. In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09). NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Carboxyhemoglobin and methemoglobin levels as prognostic markers in acute pulmonary embolism.

PubMed

Kakavas, Sotirios; Papanikolaou, Aggeliki; Ballis, Evangelos; Tatsis, Nikolaos; Goga, Christina; Tatsis, Georgios

2015-04-01

Carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels have been associated with a poor outcome in patients with various pathological conditions including cardiovascular diseases. Our aim was to retrospectively assess the prognostic value of arterial COHb and MetHb in patients with acute pulmonary embolism (PE). We conducted a retrospective study of 156 patients admitted in a pulmonary clinic due to acute PE. Measured variables during emergency department evaluation that were retrospectively analyzed included the ratio of the partial pressure of oxygen in arterial blood to the fraction of oxygen in inspired gas, Acute Physiology and Chronic Health Evaluation II score, risk stratification indices, and arterial blood gases. The association between arterial COHb and MetHb levels and disease severity or mortality was evaluated using bivariate tests and logistic regression analysis. Arterial COHb and MetHb levels correlated with Acute Physiology and Chronic Health Evaluation II and pulmonary severity index scores. Furthermore, arterial COHb and MetHb levels were associated with troponin T and N-terminal pro-B-type natriuretic peptide levels. In univariate logistic regression analysis, COHb and MetHb levels were both significantly associated with an increased risk of death. However, in multivariate analysis, only COHb remained significant as an independent predictor of in-hospital mortality. Our preliminary data suggest that arterial COHb and MetHb levels reflect the severity of acute PE, whereas COHb levels are independent predictors of in hospital death in patients in this clinical setting. These findings require further prospective validation. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular markers: a potential resource for ginger genetic diversity studies.

PubMed

Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

2016-12-01

Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

PubMed Central

Lückhoff, Hilmar K; Kruger, Frederik C; Kotze, Maritha J

2015-01-01

Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption. PMID:26019735

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

PubMed

Ooki, Akira; Maleki, Zahra; Tsay, Jun-Chieh J; Goparaju, Chandra; Brait, Mariana; Turaga, Nitesh; Nam, Hae-Seong; Rom, William N; Pass, Harvey I; Sidransky, David; Guerrero-Preston, Rafael; Hoque, Mohammad Obaidul

2017-11-15

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. Results: A methylation panel of 6 genes ( CDO1, HOXA9, AJAP1, PTGDR, UNCX , and MARCH11 ) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR , and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes. Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR . ©2017 American Association for Cancer Research.

NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer.

PubMed

Moisés, Jorge; Navarro, Alfons; Santasusagna, Sandra; Viñolas, Nuria; Molins, Laureano; Ramirez, José; Osorio, Jeisson; Saco, Adela; Castellano, Joan Josep; Muñoz, Carmen; Morales, Sara; Monzó, Mariano; Marrades, Ramón María

2017-12-13

NKX2-1, a key molecule in lung development, is highly expressed in non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma (ADK), where it is a diagnostic marker. Studies of the prognostic role of NKX2-1 in NSCLC have reported contradictory findings. Two microRNAs (miRNAs) have been associated with NKX2-1: miR-365, which targets NKX2-1; and miR-33a, which is downstream of NKX2-1. We have examined the effect of NKX2-1, miR-365 and miR-33a on survival in a cohort of early-stage NSCLC patients and in sub-groups of patients classified according to the mutational status of TP53, KRAS, and EGFR. mRNA and miRNA expression was determined using TaqMan assays in 110 early-stage NSCLC patients. TP53, KRAS, and EGFR mutations were assessed by Sanger sequencing. NKX2-1 expression was upregulated in never-smokers (P = 0.017), ADK (P < 0.0001) and patients with wild-type TP53 (P = 0.001). A negative correlation between NKX2-1 and miR-365 expression was found (ρ = -0.287; P = 0.003) but there was no correlation between NKX2-1 and miR-33a expression. Overall survival (OS) was longer in patients with high expression of NKX2-1 than in those with low expression (80.8 vs 61.2 months (P = 0.035), while a trend towards longer OS was observed in patients with low miR-365 levels (P = 0.07). The impact of NKX2-1 on OS and DFS was higher in patients with neither TP53 nor KRAS mutations. Higher expression of NKX2-1 was related to higher OS (77.6 vs 54 months; P = 0.017) and DFS (74.6 vs 57.7 months; P = 0.006) compared to low expression. The association between NKX2-1 and OS and DFS was strengthened when the analysis was limited to patients with stage I disease (P = 0.005 and P=0.003 respectively). NKX2-1 expression impacts prognosis in early-stage NSCLC patients, particularly in those with neither TP53 nor KRAS mutations.

[Diagnostic and prognostic value of heart-type fatty acid-binding protein (H-FABP), an early biochemical marker of myocardial injury].

PubMed

Bertinchant, J P; Polge, A

2005-12-01

Heart-type fatty acid-binding protein (H-FABP) is a 132 amino acids soluble protein, with general characteristics resembling myoglobin. Because of its low molecular weight (15 kd) and cytoplasmic location, it constitutes a biologic marker readily released into the circulation after myocardial injury. Despite the development of various immunoassays to measure H-FABP, few are currently easy to perform, quantitative and applicable in emergency. Most studies have shown the diagnostic sensitivity of H-FABP (i.e. its ability to detect the presence of a myocardial infarction) to be high, above that of myoglobin in patients presenting within 3 to 6 h of after the onset of chest pain. This superiority is attributable to an earlier and more rapid rise in H-FABP than in myoglobin. After thrombolysis, the serum concentrations of H-FABP peak at approximately 4 h after the onset of chest pain, and return to normal values within 24 h. Because of this rapid return of its blood concentration to baseline, H-FABP can contribute to an early biologic diagnosis of post-thrombolysis reperfusion and re-infarction. In absence of renal insufficiency, H-FABP also provides a reliable estimate of infarct size associated with ST segment elevation. When myocardial injury occurs after cardiac surgery, the second peak in H-FABP concentration precedes that of myoglobin, CK-MB or troponins. In addition, H-FABP peaks earlier and is more sensitive than troponins in the detection of subtle myocardial injury in patients presenting with acute coronary syndrome without ST segment elevation, and in patients with severe heart failure, thus offering early prognostic information. Limitations of H-FABP include a limited cardio-specificity, a narrow diagnostic window (20 to 30 h), and a nearly exclusive renal elimination.

Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

PubMed

Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

2016-01-01

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

The prognostic significance of lymphatics in colorectal liver metastases.

PubMed

Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

2014-01-01

Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

PubMed

Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

2016-11-01

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients

Distributed Prognostics based on Structural Model Decomposition

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

Investigation of Prognostic Ability of Novel Imaging Markers for Traumatic Brain Injury (TBI)

DTIC Science & Technology

2011-10-01

testing None of the above Psychological / Sociological ID: VIEW4514342955C00Name: Type of Research View: Lay Summary 1 * Provide a summary of the...best describe the current clinical status of the patient and which markers best predict a patient’s outcome status. ID: VIEW475E142D4E000Name: Lay ... Summary View: Justification, Objective, & Research Design 1 * Provide context, justification, and scientific/scholarly rationale for the study: Currently

Expression of proliferation marker Ki67 correlates to occurrence of metastasis and prognosis, histological subtypes and HPV DNA detection in penile carcinomas.

PubMed

Protzel, C; Knoedel, J; Zimmermann, U; Woenckhaus, C; Poetsch, M; Giebel, J

2007-11-01

Clinical outcome of penile squamous cell carcinoma (PSCC) largely depends on the presence of lymph node metastasis. In search of a valuable marker predicting the risk for metastasis, the expression of Ki67 was investigated immunohistochemically in primary tumors and compared to presence of inguinal lymph node metastasis. As human papilloma virus (HPV) is thought to affect Ki67 expression, we evaluated whether occurrence of HPV DNA correlates to Ki67 score or metastatic potential. Samples originated from patients subjected to resection of invasive SCC of penis. Immunohistochemistry was done on paraffin-embedded sections using a monoclonal antibody against Ki67. After DNA isolation from paraffin embedded tissue the presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Statistical analysis was done using two tail unpaired t test and Chi-square test. Four of 28 patients showed a weak Ki67 expression, without displaying lymph node metastasis. Among 17 patients showing an intermediate Ki67 index, eight exhibited metastases while in all seven patients with a strong expression of Ki67 lymph node metastases were found. The median Ki67 expression in metastastic lesions was significantly different (50.3%) from tumors without lymph node metastasis (31.8%) (p=0.024). Furthermore, a correlation between presence of HPV DNA and strong Ki67 expression was determined (p=0.009). Since our study demonstrated a strong Ki67 labeling index significantly associated to positive lymph nodes, we suggest Ki67 expression as a prognostic marker for lymph node metastasis in penile squamous carcinoma.

Expression of CD105 cancer stem cell marker in three subtypes of renal cell carcinoma.

PubMed

Saeednejad Zanjani, Leili; Madjd, Zahra; Abolhasani, Maryam; Shariftabrizi, Ahmad; Rasti, Arezoo; Asgari, Mojgan

2018-01-01

CD105 is recently described as a cancer stem cell (CSC) marker. The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.

Genetic Diversity Analysis of Medicinally Important Horticultural Crop Aegle marmelos by ISSR Markers.

PubMed

Mujeeb, Farina; Bajpai, Preeti; Pathak, Neelam; Verma, Smita Rastogi

2017-01-01

Inter simple sequence repeat (ISSR) markers help in identifying and determining the extent of genetic diversity in cultivars. Here, we describe their application in determining the genetic diversity of bael (Aegle marmelos Corr.). Universal ISSR primers are selected and their marker characteristics such as polymorphism information content, effective multiplex ratio and marker index have been evaluated. ISSR-PCR is then performed using universal ISSR primers to generate polymorphic bands. This information is used to determine the degree of genetic similarity among the bael varieties/accessions by cluster analysis using unweighted pair-group method with arithmetic averages (UPGMA). This technology is valuable for biodiversity conservation and for making an efficient choice of parents in breeding programs.

Biochemical markers and neuropsychological functioning in distal urea cycle disorders.

PubMed

Waisbren, Susan E; Cuthbertson, David; Burgard, Peter; Holbert, Amy; McCarter, Robert; Cederbaum, Stephen

2018-02-08

Urea cycle disorders often present as devastating metabolic conditions, resulting in high mortality and significant neuropsychological damage, despite treatment. The Urea Cycle Disorders Longitudinal Study is a natural history study that collects data from regular clinical follow-up and neuropsychological testing. This report examines links between biochemical markers (ammonia, glutamine, arginine, citrulline) and primary neuropsychological endpoints in three distal disorders, argininosuccinic acid synthetase deficiency (ASD or citrullinemia type I), argininosuccinic acid lyase deficiency (ASA or ALD), and arginase deficiency (ARGD). Laboratory results and test scores from neuropsychological evaluations were assessed in 145 study participants, ages 3 years and older, with ASD (n = 64), ASA (n = 65) and ARGD (n = 16). Mean full scale IQ was below the population mean of 100 ± 15 for all groups: (ASD = 79 ± 24; ASA = 71 ± 21; ARGD = 65 ± 19). The greatest deficits were noted in visual performance and motor skills for all groups. While ammonia levels remain prominent as prognostic biomarkers, other biomarkers may be equally valuable as correlates of neuropsychological functioning. Cumulative exposure to the biomarkers included in the study proved to be highly sensitive indicators of neuropsychological outcomes, even when below the cut-off levels generally considered toxic. Blood levels of biomarkers obtained on the day of neuropsychological evaluations were not correlated with measures of functioning for any disorder in any domain. The importance of cumulative exposure supports early identification and confirms the need for well-controlled management of all biochemical abnormalities (and not just ammonia) that occur in urea cycle disorders.

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors.

PubMed

Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

2017-11-01

Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. To identify a prognostic epigenetic signature in thyroid cancer. Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC. Copyright © 2017 Endocrine Society

Prognostic and predictive markers in recurrent high grade glioma; results from the BR12 randomised trial.

PubMed

Collins, Vincent Peter; Ichimura, Koichi; Di, Ying; Pearson, Danita; Chan, Ray; Thompson, Lindsay C; Gabe, Rhian; Brada, Michael; Stenning, Sally P

2014-06-20

We evaluated the prognostic and predictive value of a range of molecular changes in the setting of a randomised trial comparing standard PCV (procarbazine, CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) and vincristine) chemotherapy with the standard temozolomide (TMZ) 5-day (200 mg/m2/day) schedule and a 21-day (100 mg/m2/day) schedule in chemo-naïve, high-grade glioma (non-oligodendroglial tumours; WHO (World Health Organisation) grades III and IV) patients at first progression following radiotherapy.354 samples (79.2%) from the first operation of the 447 randomised patients provided enough tumour DNA for some or all parts of the study. Genome-wide array comparative genomic hybridisation (aCGH), mutation analysis of IDH1/2 and TP53 and methylation analyses of the MGMT CpG-island was done.84% of grade III tumours and 17% of grade IV had IDH1 or IDH2 mutations that conferred a better prognosis in both; MGMT methylation (defined as average value across 16 CpGs ≥ 10%) occurred in 75% of tumours and was also associated with improved survival. Both were of independent prognostic value after accounting for clinical factors and tumour grade. None of the molecular changes investigated gave clear evidence of a predictive benefit of TMZ over PCV or 21-day TMZ over 5-day TMZ although power was limited and a role for MGMT methylation could not be ruled out. Loss of 1p and 19q was seen in only 4 patients although hemizygous loss of 1p36 occurred in 20%.The findings support reports that IDH1/2 mutations and MGMT methylation can be used in addition to tumour grade and clinical factors to predict survival in patients with recurrent high grade gliomas when treated with any of the therapy regimes used.

Differential Prognostic Value of Coronary Computed Tomography Angiography in Relation to Exercise Electrocardiography in Asymptomatic Subjects

PubMed Central

Lee, Sang-Eun; Cho, Iksung; Hong, Geu-Ru; Sung, Ji Min; Cho, In-Jeong; Shim, Chi Young; Choi, Byoung Wook; Chung, Namsik

2015-01-01

Background To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. Methods We retrospectively enrolled 812 (59 ± 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. Results The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 ± 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). Conclusion CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA. PMID:26755933

SNP-markers in Allium species to facilitate introgression breeding in onion.

PubMed

Scholten, Olga E; van Kaauwen, Martijn P W; Shahin, Arwa; Hendrickx, Patrick M; Keizer, L C Paul; Burger, Karin; van Heusden, Adriaan W; van der Linden, C Gerard; Vosman, Ben

2016-08-31

Within onion, Allium cepa L., the availability of disease resistance is limited. The identification of sources of resistance in related species, such as Allium roylei and Allium fistulosum, was a first step towards the improvement of onion cultivars by breeding. SNP markers linked to resistance and polymorphic between these related species and onion cultivars are a valuable tool to efficiently introgress disease resistance genes. In this paper we describe the identification and validation of SNP markers valuable for onion breeding. Transcriptome sequencing resulted in 192 million RNA seq reads from the interspecific F1 hybrid between A. roylei and A. fistulosum (RF) and nine onion cultivars. After assembly, reliable SNPs were discovered in about 36 % of the contigs. For genotyping of the interspecific three-way cross population, derived from a cross between an onion cultivar and the RF (CCxRF), 1100 SNPs that are polymorphic in RF and monomorphic in the onion cultivars (RF SNPs) were selected for the development of KASP assays. A molecular linkage map based on 667 RF-SNP markers was constructed for CCxRF. In addition, KASP assays were developed for 1600 onion-SNPs (SNPs polymorphic among onion cultivars). A second linkage map was constructed for an F2 of onion x A. roylei (F2(CxR)) that consisted of 182 onion-SNPs and 119 RF-SNPs, and 76 previously mapped markers. Markers co-segregating in both the F2(CxR) and the CCxRF population were used to assign the linkage groups of RF to onion chromosomes. To validate usefulness of these SNP markers, QTL mapping was applied in the CCxRF population that segregates for resistance to Botrytis squamosa and resulted in a QTL for resistance on chromosome 6 of A. roylei. Our research has more than doubled the publicly available marker sequences of expressed onion genes and two onion-related species. It resulted in a detailed genetic map for the interspecific CCxRF population. This is the first paper that reports the detection of

Development of Novel SSR Markers for Flax (Linum usitatissimum L.) Using Reduced-Representation Genome Sequencing.

PubMed

Wu, Jianzhong; Zhao, Qian; Wu, Guangwen; Zhang, Shuquan; Jiang, Tingbo

2016-01-01

Flax ( Linum usitatissimum L.) is a major fiber and oil yielding crop grown in northeastern China. Identification of flax molecular markers is a key step toward improving flax yield and quality via marker-assisted breeding. Simple sequence repeat (SSR) markers, which are based on genomic structural variation, are considered the most valuable type of genetic marker for this purpose. In this study, we screened 1574 microsatellites from Linum usitatissimum L. obtained using reduced representation genome sequencing (RRGS) to systematically identify SSR markers. The resulting set of microsatellites consisted mainly of trinucleotide (56.10%) and dinucleotide (35.23%) repeats, with each motif consisting of 5-8 repeats. We then evaluated marker sensitivity and specificity based on samples of 48 flax isolates obtained from northeastern China. Using the new SSR panel, the results demonstrated that fiber flax and oilseed flax varieties clustered into two well separated groups. The novel SSR markers developed in this study show potential value for selection of varieties for use in flax breeding programs.

MET gene copy number gain is an independent poor prognostic marker in Korean stage I lung adenocarcinomas.

PubMed

Jin, Yan; Sun, Ping-Li; Kim, Hyojin; Seo, An Na; Jheon, Sanghoon; Lee, Choon-Taek; Chung, Jin-Haeng

2014-02-01

MET gene copy number gain (CNG) and protein overexpression have been reported in lung cancer, but the clinical implications in early stage adenocarcinoma remain unclear. We investigated MET gene copy number and protein expression in 141 cases of surgically resected stage I pulmonary adenocarcinoma. MET gene CNG was determined by silver in situ hybridization, and MET protein expression was assessed by immunohistochemistry. The correlation between MET gene CNG/protein expression and clinicopathologic parameters and prognostic significance was analyzed. MET gene CNG was found in 24.1% (34 of 141) of the cases and was associated with larger tumor size, pleural invasion, and lymphatic vessel invasion. MET gene CNG was inversely correlated with the presence of lepidic subtype (r = -0.17, p = 0.045) and was not associated with EGFR, KRAS mutation, or ALK gene rearrangement. In addition, MET gene CNG was significantly associated with shorter disease-free survival (DFS) (49 vs. 75 months; p < 0.001) and shorter overall survival (OS) (65 vs. 78 months; p = 0.01). Multivariate analysis confirmed that MET gene CNG was significantly associated with poorer DFS [p < 0.001; hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.2-13.9] but was not significantly associated with OS. MET overexpression was observed in 71.3% of cases (97 of 136), but it was not correlated with gene CNG. MET gene CNG is an independent poor prognostic factor in patients with stage I lung adenocarcinoma. It is associated with aggressive pathologic features and is inversely correlated with the presence of lepidic subtype.

Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis

PubMed Central

Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming

2015-01-01

Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID:26549923

Prognostic significance of muc4 expression in gallbladder carcinoma.

PubMed

Lee, Hyeon Kook; Cho, Min-Sun; Kim, Tae Hun

2012-10-27

Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.

Prognostic significance of muc4 expression in gallbladder carcinoma

PubMed Central

2012-01-01

Background Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. Methods The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. Results For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). Conclusions MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression. PMID:23101681

[The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

PubMed

Szarvas, Tibor

2009-12-01

Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

PubMed Central

Kim, Kyungbin; Park, Won Young; Kim, Jee Yeon; Sol, Mee Young; Shin, Dong Hun; Park, Do Youn; Lee, Chang Hun; Lee, Jeong Hee

2012-01-01

Background Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy. PMID:23323103

Optimal marker placement in hadrontherapy: intelligent optimization strategies with augmented Lagrangian pattern search.

PubMed

Altomare, Cristina; Guglielmann, Raffaella; Riboldi, Marco; Bellazzi, Riccardo; Baroni, Guido

2015-02-01

In high precision photon radiotherapy and in hadrontherapy, it is crucial to minimize the occurrence of geometrical deviations with respect to the treatment plan in each treatment session. To this end, point-based infrared (IR) optical tracking for patient set-up quality assessment is performed. Such tracking depends on external fiducial points placement. The main purpose of our work is to propose a new algorithm based on simulated annealing and augmented Lagrangian pattern search (SAPS), which is able to take into account prior knowledge, such as spatial constraints, during the optimization process. The SAPS algorithm was tested on data related to head and neck and pelvic cancer patients, and that were fitted with external surface markers for IR optical tracking applied for patient set-up preliminary correction. The integrated algorithm was tested considering optimality measures obtained with Computed Tomography (CT) images (i.e. the ratio between the so-called target registration error and fiducial registration error, TRE/FRE) and assessing the marker spatial distribution. Comparison has been performed with randomly selected marker configuration and with the GETS algorithm (Genetic Evolutionary Taboo Search), also taking into account the presence of organs at risk. The results obtained with SAPS highlight improvements with respect to the other approaches: (i) TRE/FRE ratio decreases; (ii) marker distribution satisfies both marker visibility and spatial constraints. We have also investigated how the TRE/FRE ratio is influenced by the number of markers, obtaining significant TRE/FRE reduction with respect to the random configurations, when a high number of markers is used. The SAPS algorithm is a valuable strategy for fiducial configuration optimization in IR optical tracking applied for patient set-up error detection and correction in radiation therapy, showing that taking into account prior knowledge is valuable in this optimization process. Further work will be

Prognostic categories and timing of negative prognostic communication from critical care physicians to family members at end-of-life in an intensive care unit.

PubMed

Gutierrez, Karen M

2013-09-01

Negative prognostic communication is often delayed in intensive care units, which limits time for families to prepare for end-of-life. This descriptive study, informed by ethnographic methods, was focused on exploring critical care physician communication of negative prognoses to families and identifying timing influences. Prognostic communication of critical care physicians to nurses and family members was observed and physicians and family members were interviewed. Physician perception of prognostic certainty, based on an accumulation of empirical data, and the perceived need for decision-making, drove the timing of prognostic communication, rather than family needs. Although prognoses were initially identified using intuitive knowledge for patients in one of the six identified prognostic categories, utilizing decision-making to drive prognostic communication resulted in delayed prognostic communication to families until end-of-life (EOL) decisions could be justified with empirical data. Providers will better meet the needs of families who desire earlier prognostic information by separating prognostic communication from decision-making and communicating the possibility of a poor prognosis based on intuitive knowledge, while acknowledging the uncertainty inherent in prognostication. This sets the stage for later prognostic discussions focused on EOL decisions, including limiting or withdrawing treatment, which can be timed when empirical data substantiate intuitive prognoses. This allows additional time for families to anticipate and prepare for end-of-life decision-making. © 2012 John Wiley & Sons Ltd.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464