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Sample records for cancer prognostic implications

  1. Nodal metastases in thyroid cancer: prognostic implications and management.

    PubMed

    Wang, Laura Y; Ganly, Ian

    2016-04-01

    The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.

  2. [Immune response and digestive cancers: Prognostic and therapeutic implications].

    PubMed

    Bibeau, Frédéric; Bazille, Céline; Svrcek, Magali; Pierson, Rémi; Lagorce-Pagès, Christine; Cohen, Romain; André, Thierry

    2017-02-01

    The aim of this article is to emphasize the impact of the immune response in digestive cancers, especially from colorectal (CRC) origin. In this setting, an adaptive lymphocytic infiltrate underlines the prognostic impact of the immune response, because it is associated to a favorable outcome. The next challenge will be to validate, in a prospective therapeutic trial, the integration of the immune response as decisional parameter for adjuvant therapy. The immune response is also a predictive parameter in microsatellite instable metastatic CRC, characterized by an adaptive lymphocytic infiltrate, leading to a very high response rate to immune therapies. However, prognostic and predictive biomarkers still need to be optimized in order to better select patients. These data are also valuable for digestive non-colorectal cancers, which are briefly analyzed. The methodology for the assessment of these prognostic and predictive biomarkers, which represents an important issue in precision medicine, is also discussed.

  3. Prognostic implication of hepatoduodenal ligament lymph nodes in gastric cancer

    PubMed Central

    Oh, Sung Eun; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

    2017-01-01

    Abstract There has been controversy regarding whether hepatoduodenal lymph node (HDLN) metastasis in gastric cancer is distant or regional metastasis. HDLN positivity was classified as distant metastasis in the 7th American Joint Committee on Cancer (AJCC) classification, but it was reclassified as regional lymph node metastasis in the 8th AJCC classification. The aim of our study is to verify prognostic significance of HDLN metastasis in gastric cancer. This retrospective study enrolled patients with gastric cancer who underwent D2 gastrectomy from January 2007 to June 2010. HDLN was classified as a regional lymph node. Total number of patients was 3175; 143 (4.5%) of them had HDLN metastasis. The HDLN positivity was significantly associated with older age, more advanced tumor stage, undifferentiated histologic type, and pathologic diagnosis of lymphatic, vascular, and perineural invasions. Five-year survival rate of HDLN-positive patients with stages I to III disease was significantly higher than that of stage IV group (59.3% vs 18.8%, P = 0.001). In patients with stage III disease, 5-year survival rate of HDLN-positive group was significantly lower than that of HDLN-negative group (51.7% vs 66.3%, P = 0.001). Multivariate analysis showed that HDLN metastasis was an independent prognostic factor. HDLN has a different prognostic significance from other regional lymph nodes in advanced stage of gastric cancer though its positivity is not considered as distant metastasis. HDLN positivity itself seems to be an independent prognostic factor in gastric cancer, and the survival outcomes of patients with stage III disease need to be reconsidered according to HDLN positivity. PMID:28353581

  4. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  5. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    PubMed

    Lau, Yat Ming; Cheung, Tak Hong; Yeo, Winnie; Mo, Frankie; Yu, Mei Yung; Lee, Kun Min; Ho, Wendy C S; Yeung, Apple C M; Law, Priscilla T Y; Chan, Paul K S

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  6. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

    PubMed Central

    Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2015-01-01

    The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

  7. Syndecan-1 in Cancer: Implications for Cell Signaling, Differentiation, and Prognostication

    PubMed Central

    Szatmári, Tünde; Ötvös, Rita; Hjerpe, Anders; Dobra, Katalin

    2015-01-01

    Syndecan-1, a cell surface heparan sulfate proteoglycan, is critically involved in the differentiation and prognosis of various tumors. In this review, we highlight the synthesis, cellular interactions, and the signalling pathways regulated by syndecan-1. The basal syndecan-1 level is also crucial for understanding the sequential changes involving malignant transformation, tumor progression, and advanced or disseminated cancer stages. Moreover, we focus on the cellular localization of this proteoglycan as cell membrane anchored and/or shed, soluble syndecan-1 with stromal or nuclear accumulation and how this may carry different, highly tissue specific prognostic information for individual tumor types. PMID:26420915

  8. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications

    PubMed Central

    Czerewaty, Michał; Deskur, Anna; Safranow, Krzysztof; Urasińska, Elżbieta; Starzyńska, Teresa

    2016-01-01

    Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. PMID:27635108

  9. Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer

    PubMed Central

    2014-01-01

    Background The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in not only cell motility, cell adhesion, and apoptosis, but also in various cell signaling pathways. Phosphorylation at Thr-567 and Tyr-353 are key regulatory events in the transition of the dormant to active form of ezrin. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC). Methods Ezrin and p-ezrin protein expressions were examined by immunohistochemistry in 150 NSCLC and adjacent non-tumor tissues and 14 normal lung tissues. qRT-PCR was used to determine ezrin mRNA expression levels in fresh tissues. The correlations between overexpression of ezrin and p-ezrin and the clinicopathological features of NSCLC were analyzed. The survival rates were calculated by the Kaplan-Meier method for 108 NSCLC cases. Results Ezrin and ezrinThr-567 proteins showed cytosolic and membranous staining patterns; however, ezrinTyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrinThr-567, and ezrinTyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrinThr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrinThr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrinThr-567 were associated with shortened survival time for patients with early stage NSCLC. Conclusions Ezrin and p-ezrin, especially ezrinThr-567, may prove to be useful as a novel prognostic biomarker of NSCLC. PMID:24629131

  10. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

    Huang, Jie; Hu, Wei; Sood, Anil K

    2014-01-01

    Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

  11. Clinical Implications of Systemic Inflammatory Response Markers as Independent Prognostic Factors in Colorectal Cancer Patients

    PubMed Central

    Paik, Kwang Yeol; Lee, Yoon Suk; Sung, Na Young; Kwon, Taek Soo

    2014-01-01

    Purpose Cancer-related inflammation affects many aspects of malignancy. We confirm the effects of early postoperative systemic inflammation on cancer prognosis. Materials and Methods Six hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009. Measurements of white blood cells, neutrophils, lymphocytes, monocytes, and platelet counts were performed preoperatively, daily until the fourth postoperative day, and subsequently every two days. Patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm3 after surgery. Results Preoperative white blood cell (WBC) counts correlated with stage of disease. In univariate survival analyses, tumor, node, metastasis (TNM) stage, and monocyte count were associated with cancer-free survival. In addition, cancer-free survival outcomes were worse in patients who required more than four days for the normalization of WBC count. A TNM stage greater than II and the neutrophil lymphocyte ratio were associated with the duration of overall survival. In a multivariate analysis of these significant variables, TNM stage, an interval longer than four days for normalization of WBC counts and monocyte count independently associated with cancer-free survival. Conclusion Postoperative early inflammatory phase and preoperative monocyte count correlate with poor colon cancer prognosis. We can conclude that preoperative and postoperative inflammatory response and period unfavorably affect the metastatic microenvironment. PMID:24520225

  12. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  13. Colon cancer and gene alterations: their immunological implications and suggestions for prognostic indices and improvements in biotherapy.

    PubMed

    Contasta, Ida; Pellegrini, Patrizia; Berghella, Anna Maria; Del Beato, Tiziana; Adorno, Domenico

    2006-10-01

    Studies have shown that changes occur in c-Ki-ras, p53, and Bcl2 gene structure and function during the various stages of human colon carcinogenesis. Alterations of these genes are responsible for the establishment of a state of continuous stimulus for cell division and apoptotic inhibition at physiological and pharmacological levels. This paper focuses on the results of our research aimed at investigating how these gene alterations influence tumoral mechanisms on an immunological level and how immunological parameters can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. Overall, our data suggest that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response, determining an impairment of immune cell activation at both antigen- presenting-cell and T-cell levels. c-Ki-ras gene mutations, p53 deletions, and Bc12 expression, on the other hand, can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. The p53 oncogene does not appear to impair patients' immunological response further. In conclusion, an evaluation of c-Ki-ras, rather than p53 gene alterations, would seem to be more relevant in colon cancer prevention programs and biotherapy improvement.

  14. Angiogenesis: a prognostic determinant in pancreatic cancer?

    PubMed

    van der Zee, Jill A; van Eijck, Casper H J; Hop, Wim C J; van Dekken, Herman; Dicheva, Bilyana M; Seynhaeve, Ann L B; Koning, Gerben A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2011-11-01

    Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

  15. Autophagy-related prognostic signature for breast cancer.

    PubMed

    Gu, Yunyan; Li, Pengfei; Peng, Fuduan; Zhang, Mengmeng; Zhang, Yuanyuan; Liang, Haihai; Zhao, Wenyuan; Qi, Lishuang; Wang, Hongwei; Wang, Chenguang; Guo, Zheng

    2016-03-01

    Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy-related prognostic signature for breast cancer. Based on the autophagy-related signature, the training dataset GSE21653 could be classified into high-risk and low-risk subgroups with significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P = 1.37 × 10(-5)). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy-related signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI = (1.48, 3.03); P = 1.65 × 10(-3)) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P = 9.95 × 10(-4)). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis-free survival for breast cancer.

  16. Hypermethylation of BRCA1 gene: implication for prognostic biomarker and therapeutic target in sporadic primary triple-negative breast cancer.

    PubMed

    Zhu, X; Shan, L; Wang, F; Wang, J; Wang, F; Shen, G; Liu, X; Wang, B; Yuan, Y; Ying, J; Yang, H

    2015-04-01

    Paraffin sections from 239 cases of surgical resected mammary gland carcinomas were assessed to determine the role of BRCA1 gene methylation in sporadic triple-negative breast cancer and to evaluate the relationship between BRCA1 gene methylation and clinicopathologic features of triple-negative breast cancer in the National Cancer Center, China. Diagnostic tissues collected from patients received mastectomy in the National Cancer Center from January 1, 1999 to December 31, 2008 were reviewed. Tissue microarrays were constructed using 239 triple-negative breast cancer cases and stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor. Methylation status of the BRCA1 promoter was measured by methylation-specific PCR and analyzed against clinicopathologic characteristics, subtypes, and prognosis using standard statistical methods. Among the 239 triple-negative breast cancer cases, 137 (57.3 %) showed methylation of the BRCA1. According to the immunohistochemistry results, triple-negative breast cancer cases were classified into basal-like breast cancer (60.7 %) and non-basal-like breast cancer (39.3 %). The frequency of BRCA1 methylation was significantly higher in basal-like breast cancer subtype (71.7 %) than the non-basal subtype (35.1 %). Thus, BRCA1 methylation is statistically significantly correlated with basal-like breast cancer subtype (p < 0.001). Multivariate analyses further showed that BRCA1 promoter methylation is an independently predictor of overall survival (p = 0.023; HR 2.32; 95 % CI 1.12-4.81) and disease-free survival (p = 0.022; HR 2.36; 95 % CI 1.13-4.90) in triple-negative breast cancer. Here we demonstrated that epigenetic alteration of key tumor suppressor gene can be a promising biomarker for the prognosis of triple-negative breast cancer/basal-like breast cancer. Specifically our finding revealed that BRCA1 methylation is closely associated with a

  17. Diagnostic and prognostic epigenetic biomarkers in cancer.

    PubMed

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  18. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer *

    PubMed Central

    Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; de Castro, Gilberto

    2015-01-01

    Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC. PMID:26398757

  19. The prognostic implications of macrophages expressing proliferating cell nuclear antigen in breast cancer depend on immune context.

    PubMed

    Campbell, Michael J; Wolf, Denise; Mukhtar, Rita A; Tandon, Vickram; Yau, Christina; Au, Alfred; Baehner, Frederick; van't Veer, Laura; Berry, Donald; Esserman, Laura J

    2013-01-01

    Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA(+) TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA(+) TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA(+) TAM levels were associated with more M1- than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA(+) TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA(+) TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA(+) TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA(+) TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer.

  20. RON is not a prognostic marker for resectable pancreatic cancer

    PubMed Central

    2012-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:22958871

  1. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication

    PubMed Central

    Islam, Saimul; Dasgupta, Hemantika; Roychowdhury, Anirban; Bhattacharya, Rittwika; Mukherjee, Nupur; Roy, Anup; Mandal, Gautam Kumar; Alam, Neyaz; Biswas, Jaydip; Mandal, Shyamsundar; Roychoudhury, Susanta

    2017-01-01

    Objectives Human papillomavirus (HPV) causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC) too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT) and Neo-adjuvant chemotherapy (NACT) patients with subsequent analysis of HPV profile. Methods HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein) of the prevalent subtype was done. Results High prevalence of HPV was observed in both PT (64.0%) and NACT (71.0%) cases with significant association with younger (20–45 yrs) PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21), fibro adenomas (30%, 3/10) to tumors (64.8%, 203/313) samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0%) followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839) in the LCR region and two (KT020836 and KT020837) in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314) and E6^E7*II (KU199315) fusion transcript variants. Conclusion Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients. PMID:28245287

  2. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  3. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  4. Prognostic Value and Implication for Chemotherapy Treatment of ABCB1 in Epithelial Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Yang, Qiang; Zhu, Yapei; Zhao, Simei; Wang, Zehua

    2016-01-01

    Background Chemotherapy resistance is reported to correlate with up-regulation of anti-tumor agent transporter ABCB1 (p-gp) in epithelial ovarian cancer (EOC), but the results remain controversial. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association between high ABCB1 status or ABCB1 gene variants and overall survival (OS), progression free survival (PFS), and total response rate (TR) in patients with EOC. Materials and Methods Electronic searches were performed using Pubmed, EMBASE, Web of Science and Chinese Wanfang databases from January 1990 to February 2016. Summary hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (CIs) were combined using fixed or random-effects models as appropriate. Results Thirty-eight retrospective studies of 8607 cases qualified for meta-analysis were identified. Our results suggested that ABCB1 over-expression was significantly associated with unfavorable OS (HR = 1.54; 95% CI, 1.25–1.90), PFS (HR = 1.49; 95% CI, 1.22–1.82) and TR (RR = 0.63; 95% CI, 0.54–0.75). After adjustment for age, clinical stage, residual disease, histological type and tumor grade, high ABCB1 status remained to be a significant risk factor for adverse OS and PFS. Patients with recurrent ABCB1 positivity suffered from poorer OS than those with primary ABCB1 positivity. However, stratified by chemotherapy regimen, inverse correlation between high ABCB1 status and poor OS, PFS and TR were only found in patients underwent platinum-based chemotherapy but not in patients received standard platinum/paclitaxel-based chemotherapy. No evidence was found for any association between ABCB1 gene polymorphisms and OS, PFS or TR. Conclusion High ABCB1 status is significantly associated with chemo-resistance and poor prognosis in patients with EOC. Large-scale, prospective studies are needed to assess the clinical value of ABCB1 expression in EOC more accurately. PMID:27812204

  5. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis

    PubMed Central

    Luchini, Claudio; Veronese, Nicola; Solmi, Marco; Cho, Hanbyoul; Kim, Jae-Hoon; Chou, Angela; Gill, Anthony J.; Faraj, Sheila F.; Chaux, Alcides; Netto, George J.; Nakayama, Kentaro; Kyo, Satoru; Lee, Soo Young; Kim, Duck-Woo; Yousef, George M.; Scorilas, Andreas; Nelson, Gregg S.; Köbel, Martin; Kalloger, Steve E.; Schaeffer, David F.; Yan, Hai-Bo; Liu, Feng; Yokoyama, Yoshihito; Zhang, Xianyu; Pang, Da; Lichner, Zsuzsanna; Sergi, Giuseppe; Manzato, Enzo; Capelli, Paola; Wood, Laura D.; Scarpa, Aldo; Correll, Christoph U.

    2015-01-01

    Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A−) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A−, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A− adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A−: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A− significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19–2.00, I2 = 31%). Using HRs adjusted for potential confounders, ARID1A− was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19–5.45, I2 = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22–3.05, I2 = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment. PMID:26384299

  6. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis.

    PubMed

    Luchini, Claudio; Veronese, Nicola; Solmi, Marco; Cho, Hanbyoul; Kim, Jae-Hoon; Chou, Angela; Gill, Anthony J; Faraj, Sheila F; Chaux, Alcides; Netto, George J; Nakayama, Kentaro; Kyo, Satoru; Lee, Soo Young; Kim, Duck-Woo; Yousef, George M; Scorilas, Andreas; Nelson, Gregg S; Köbel, Martin; Kalloger, Steve E; Schaeffer, David F; Yan, Hai-Bo; Liu, Feng; Yokoyama, Yoshihito; Zhang, Xianyu; Pang, Da; Lichner, Zsuzsanna; Sergi, Giuseppe; Manzato, Enzo; Capelli, Paola; Wood, Laura D; Scarpa, Aldo; Correll, Christoph U

    2015-11-17

    Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A- adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A-: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A- significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19-2.00, I(2) = 31%). Using HRs adjusted for potential confounders, ARID1A- was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19-5.45, I(2) = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22-3.05, I(2) = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment.

  7. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2013-10-01

    aims. Ethics approval has been obtained for the samples collection of AIM1. The chromosome 16p13.3 gain was found to be associated with high Gleason...Prostate cancer, Genomic alteration, Fluorescence in situ hybridization (FISH), Prognostic markers, ectopic expression, gene silencing, cDNA cloning ...In regard to AIM1 and AIM2, we have recently obtained the final approval from the Ethics committee of our hospital after a lengthy process. We have

  8. [Prognostic factors of early breast cancer].

    PubMed

    Almagro, Elena; González, Cynthia S; Espinosa, Enrique

    2016-02-19

    Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies.

  9. [Prognostic implications of GP3a glucoprotein gene PLA1/PLA2 allele in prostatic cancer: pilot results of the study].

    PubMed

    Loran, O B; Itkes, A V; Seregin, A A; Miandina, G I

    2005-01-01

    We studied the role of integrins, primarily, the role of allele distribution of GP3a gene in development of prostatic cancer (PC) and assessment of its prognostic significance. From November 2003 to May 2004 we examined 32 patients with PC: 11 patients with local PC T1-2N0M0; 14 patients with locally advanced cancer T3N0M0 and 7 patients with invasive and/or metastatic cancer T3-4N10-1 or T3-4N0-1M1. The blood from all the patients we studied with PCR for alleles of GP3a gene, PSA. Seventeen patients were found to have alleles PLA1A1, 14(44%)--alleles PLA1A2, 1(3%)--alleles PLA2A2. Alleles PLA1A2 occurred significantly more often than in the population (p < 0.005). The group analysis has found that 8 patients with local PC had alleles PLA1A1, 3 patients--alleles PLA1A2 (27%). We discovered alleles PLA2A2, PLA1A1 and PLA1A2 in 1(7%), 5(36%) and 8(57%) patients with locally advanced PC, respectively. Among patients with metastatic and/or invasive prostatic cancer, there were 4 (57%) and 3 (43%) cases of alleles PLA1A1 and PLA1A2, respectively. Our study demonstrated influence of carriage of PLA2 allele on occurrence of PC risk (5-fold higher) and its invasive forms (10-fold higher and more). Probability to develop local invasion among patients with prostatic cancer--carriers allele PLA1A2 is 6 times higher than among carriers of alleles PLA1A1. A PC course in carriers of alleles PLA1A2 may be characterized by faster development of local invasion and metastasizing vs carriers of alleles PLA1A1. These findings can be used in design of nomograms for prognostication of invasion of clinically small tumors in verification of significance on greater number of the patients.

  10. Novel Prostate Cancer Pathway Modeling using Boolean Implication

    DTIC Science & Technology

    2012-09-01

    standard diagnostic marker for prostate cancer despite its serious limitations. Large proportions of men are being diagnosed with prostate cancer but...recent studies imply that many of them don’t need prostate cancer treatment. There is clearly a need for better diagnostic and prognostic marker in...discovery of better diagnostic and prognostic markers . Body Previously, we have published a novel approach to discover Boolean implications

  11. Elovl6 is a poor prognostic predictor in breast cancer

    PubMed Central

    FENG, YIN-HSUN; CHEN, WEI-YU; KUO, YU-HSUAN; TUNG, CHAO-LING; TSAO, CHAO-JUNG; SHIAU, AI-LI; WU, CHAO-LIANG

    2016-01-01

    Elongation of long chain fatty acids family member 6 (Elovl6) has been demonstrated to be involved in insulin resistance, obesity and lipogenesis. In addition, it has been reported that the protein is upregulated in human hepatocellular carcinoma and is implicated in nonalcoholic steatohepatitis-associated liver carcinogenesis. Excess body weight has been associated with an increased risk of postmenopausal breast cancer and poor prognosis. However, the connection between Elovl6 expression and outcome of breast cancer remains uncertain. Therefore, the present study used immunohistochemical analysis to investigate the expression of Elovl6 in breast cancer tissues from patients who had undergone curative mastectomy. Out of a total of 70 patients, 37.1% of patients exhibited positive Elovl6 expression in breast cancer tissue, whilst 62.9% were considered as negative. Positive Elov16 expression correlated with positive lymph node involvement and shorter recurrence-free survival. However, Elovl6 expression had no association with primary tumor size, lymph node metastasis, stage, grade, estrogen receptor, progesterone receptor, HER2 and age. Therefore, positive Elovl6 expression is a poor prognostic factor in patients with breast cancer that have previously undergone surgery, and may function as a potential therapeutic approach in the future, particularly in the scope of obesity related disease. PMID:27347126

  12. Specimen banks for cancer prognostic factor research.

    PubMed

    Burke, H B; Henson, D E

    1998-10-01

    Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research.

  13. Prognostic factors for patients with hepatic metastases from breast cancer.

    PubMed

    Wyld, L; Gutteridge, E; Pinder, S E; James, J J; Chan, S Y; Cheung, K L; Robertson, J F R; Evans, A J

    2003-07-21

    Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

  14. CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

    PubMed Central

    Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

    2017-01-01

    The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway. PMID:27885175

  15. Insights into Orphan Nuclear Receptors as Prognostic Markers and Novel Therapeutic Targets for Breast Cancer

    PubMed Central

    Aesoy, Reidun; Clyne, Colin D.; Chand, Ashwini L.

    2015-01-01

    There is emerging evidence asserting the importance of orphan nuclear receptors (ONRs) in cancer initiation and progression. In breast cancer, there is a lot unknown about ONRs in terms of their expression profile and their transcriptional targets in the various stages of tumor progression. With the classification of breast tumors into distinct molecular subtypes, we assess ONR expression in the different breast cancer subtypes and with patient outcomes. Complementing this, we review evidence implicating ONR-dependent molecular pathways in breast cancer progression to identify candidate ONRs as potential prognostic markers and/or as therapeutic targets. PMID:26300846

  16. Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms

    PubMed Central

    Zhou, Yi-Xin; Wang, Feng; Zhang, Dong-Sheng; Wang, Feng-Hua; Li, Yu-Hong; Xu, Rui-Hua

    2016-01-01

    The present study aimed to evaluate the prognostic significance of preoperative serum lactate dehydrogenase (SLDH) levels for resected gastric cancer and construct prognostic nomograms for risk prediction. The study cohort consisted of 619 patients with D2-resected gastric cancer. The relationship of SLDH levels with clinicopathological features and clinical outcomes was evaluated. Prognostic nomograms were created using identified prognosticators to predict 3-year overall survival (OS) and 3-year disease-free survival (DFS), and bootstrap validation was performed. High SLDH levels were correlated with old age but not depth of invasion or lymph node metastasis. When assessed as a continuous variable, high SLDH levels were independently associated with poor OS and DFS. Internal validation of the developed nomograms revealed good predictive accuracy (bootstrap-corrected concordance indices: 0.77 and 0.75, respectively for prediction of OS and DFS). The preoperative SLDH levels, an identified unfavorable prognosticator, were incorporated into nomograms along with other clinicopathological features to refine the prediction of clinical outcomes for patients with D2-resected gastric cancer. PMID:27223065

  17. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  18. The 70-Gene Prognostic Signature for Korean Breast Cancer Patients

    PubMed Central

    Na, Kuk Young; Lee, Jeong Eon; Kim, Hee Jeong; Yang, Jung-Hyun; Ahn, Sei-Hyun; Moon, Byung-In; Kim, Ra Mi; Ko, Si Mon; Jung, Yong Sik

    2011-01-01

    Purpose A 70-gene prognostic signature has prognostic value in patients with node-negative breast cancer in Europe. This diagnostic test known as "MammaPrint™ (70-gene prognostic signature)" was recently validated and implementation was feasible. Therefore, we assessed the 70-gene prognostic signature in Korean patients with breast cancer. We compared the risk predicted by the 70-gene prognostic signature with commonly used clinicopathological guidelines among Korean patients with breast cancer. We also analyzed the 70-gene prognostic signature and clinicopathological feature of the patients in comparison with a previous validation study. Methods Forty-eight eligible patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals in Korea. Fresh tumor samples were analyzed with a customized microarray for the 70-gene prognostic signature. Concordance between the risk predicted by the 70-gene prognostic signature and risk predicted by commonly used clinicopathological guidelines (St. Gallen guidelines, National Institutes of Health [NIH] guideline, and Adjuvant! Online) was evaluated. Results Prognosis signatures were assessed in 36 patients. No significant differences were observed in the clinicopathological features of patients compared with previous studies. The 70-gene prognosis signature identified five (13.9%) patients with a low-risk prognosis signature and 31 (86.1%) patients with a high-risk prognosis signature. Clinical risk was concordant with the prognosis signature for 29 patients (80.6%) according to the St. Gallen guidelines; 30 patients (83.4%) according to the NIH guidelines; and 23 patients (63.8%) according to the Adjuvant! Online. Our results were different from previous validation studies in Europe with about a 40% low-risk prognosis and about a 60% high-risk prognosis. The high incidence in the high-risk group was consistent with data in Japan. Conclusion The results of 70-gene prognostic signature of Korean patients with

  19. Prognostic Relevance and Function of MSX2 in Colorectal Cancer

    PubMed Central

    Liu, Jiancheng; An, Huaying; Yuan, Wei; Feng, Qiang

    2017-01-01

    Colorectal cancer patients with diabetes had the high risks of total mortality. High expression of MSX2 is related to development of diabetes. There are few reports about the clinical implications and function of MSX2 in colorectal cancer (CRC). The purpose of this study is to investigate the relationship between the expression of MSX2 and clinical relevance and discover the possible mechanism of MSX2 in the development of CRC. Compared with adjacent tissues, the expression of MSX2 was higher in tumor tissues in both mRNA and protein levels (P < 0.01). Kaplan-Meier survival analysis showed that high mRNA expression of MSX2 was associated with short survival time (P = 0.013). Chi-squared test analysis indicated that MSX2 expression was related to tumor size (P = 0.04), tumor locus (P = 0.025), clinical stage (P < 0.001), tumor invasion (P = 0.003), lymphatic metastasis (P = 0.01), and distant metastasis (P = 0.033). In vitro experiments demonstrated that knockdown of MSX2 expression attenuated cell proliferation and invasion, promoted cell cycle arrest and apoptosis, and inactivated Akt phosphorylation. In conclusion, MSX2 played a crucial role in the progression of CRC and may be a potential novel prognostic factor and therapeutic target for CRC therapy. Our work may provide certain enlightenment for investigating the mechanism of MSX2 in the process of diabetes. PMID:28286778

  20. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker.

    PubMed

    Zhang, Lahong; Chen, Zhaojun; Xue, Dan; Zhang, Qi; Liu, Xiyong; Luh, Frank; Hong, Liquan; Zhang, Hang; Pan, Feng; Liu, Yuhua; Chu, Peiguo; Zheng, Shu; Lou, Guoqiang; Yen, Yun

    2016-11-01

    Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery.

  1. Distinct prognostic values of S100 mRNA expression in breast cancer

    PubMed Central

    Zhang, Shizhen; Wang, Zhen; Liu, Weiwei; Lei, Rui; Shan, Jinlan; Li, Ling; Wang, Xiaochen

    2017-01-01

    S100 family genes encode low molecular weight, acidic-Ca2+ binding proteins implicating in a wide spectrum of biological processes. S100 family contains at least 20 members, most of which are frequently dysregulated in human malignancies including breast cancer. However, the prognostic roles of each individual S100, especially the mRNA level, in breast cancer patients remain elusive. In the current study, we used “The Kaplan-Meier plotter” (KM plotter) database to investigate the prognostic values of S100 mRNA expression in breast cancer. Our results indicated that high mRNA expression of S100A8, S100A9, S100A11 and S100P were found to be significantly correlated to worse outcome, while S100A1 and S100A6 were associated with better prognosis in all breast cancer patients. We further assessed the prognostic value of S100 in different intrinsic subtypes and clinicopathological features of breast cancer. The associated results will elucidate the role of S100 in breast cancer and may further lead the research to explore the S100-targeting reagents for treating breast cancer patients. PMID:28051137

  2. Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination

    PubMed Central

    Nie, Runcong; Yuan, Shuqiang; Chen, Shi; Chen, Xiaojiang; Chen, Yongming; Zhu, Baoyan; Qiu, Haibo; Zhou, Zhiwei; Peng, Junsheng; Chen, Yingbo

    2016-01-01

    Objective The predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination. Methods A total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. Results Compared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362). Conclusions PNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients. PMID:28174485

  3. Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications.

    PubMed

    Henry, P C; Evans, A J

    2009-07-01

    Intraductal carcinoma of the prostate (IDCP) has been described as a lesion associated with poor prognostic features in prostate cancer. Its recognition and reporting in prostate specimens, particularly in needle biopsies, is critical as it carries significant implications for patient management. Recent histological definitions have been proposed to assist in the recognition of IDCP and to help distinguish it from lesions with similar appearance, but different clinical behaviour. In this review, a historical overview of the description of IDCP will be presented followed by a summary of the current histological diagnostic criteria and the recommendations for management and reporting of IDCP.

  4. Prognostic values of Notch receptors in breast cancer.

    PubMed

    Xu, Junming; Song, Fangbin; Jin, Tao; Qin, Jun; Wu, Junyi; Wang, Min; Wang, Ye; Liu, Jun

    2016-02-01

    Notch receptors are frequently deregulated in several human malignancies including human breast cancer. Activation of Notch has been reported to cause mammary carcinomas in mice. However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. In the current study, we investigated the prognostic value of Notch receptors in human BC patients. More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. Our results showed that Notch1 messenger RNA (mRNA) high expression was correlated to worsen overall survival (OS) in PgR-negative BC patients. Notch2, Notch3, and Notch4 mRNA high expressions were found to be correlated to better OS for all breast cancer patients. Notch2 was also found to be correlated to better OS in lymph node-negative breast cancer patients and HER2-positive breast cancer patients. These results will be useful for better understanding of the heterogeneity and complexity in the molecular biology of breast cancer and for developing tools to more accurately predict their prognosis and design their customized treatment strategies.

  5. Prognostic significance of tumour stroma ratio in inflammatory breast cancer.

    PubMed

    Downey, Candice L; Thygesen, Helene H; Sharma, Nisha; Shaaban, Abeer M

    2015-01-01

    Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size.

  6. Validation of Metabolomic, Diagnostic, and Prognostic Classifiers of Lung Cancer

    DTIC Science & Technology

    2016-10-01

    which may aid currently existing risk, diagnostic and prognostic lung cancer classifiers in the military populations. 15. SUBJECT TERMS 16...was sub-contracted as a biostatistician to aid in data analysis and interpretation, and his extensive expertise will be utilized and will be crucial...databases; • biospecimen collections; • audio or video products; • software; • models; • educational aids or

  7. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2014-10-01

    Assessment post- Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict early...operative PSA levels, GS, T-Stage and CAPRA -S risk scores respectively, improved the overall prognostication in these patients (log rank, Pɘ.001...Risk Assessment post-Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict

  8. Predicting cancer prognosis using interactive online tools: a systematic review and implications for cancer care providers.

    PubMed

    Rabin, Borsika A; Gaglio, Bridget; Sanders, Tristan; Nekhlyudov, Larissa; Dearing, James W; Bull, Sheana; Glasgow, Russell E; Marcus, Alfred

    2013-10-01

    Cancer prognosis is of keen interest for patients with cancer, their caregivers, and providers. Prognostic tools have been developed to guide patient-physician communication and decision-making. Given the proliferation of prognostic tools, it is timely to review existing online cancer prognostic tools and discuss implications for their use in clinical settings. Using a systematic approach, we searched the Internet, Medline, and consulted with experts to identify existing online prognostic tools. Each was reviewed for content and format. Twenty-two prognostic tools addressing 89 different cancers were identified. Tools primarily focused on prostate (n = 11), colorectal (n = 10), breast (n = 8), and melanoma (n = 6), although at least one tool was identified for most malignancies. The input variables for the tools included cancer characteristics (n = 22), patient characteristics (n = 18), and comorbidities (n = 9). Effect of therapy on prognosis was included in 15 tools. The most common predicted outcome was cancer-specific survival/mortality (n = 17). Only a few tools (n = 4) suggested patients as potential target users. A comprehensive repository of online prognostic tools was created to understand the state-of-the-art in prognostic tool availability and characteristics. Use of these tools may support communication and understanding about cancer prognosis. Dissemination, testing, refinement of existing, and development of new tools under different conditions are needed.

  9. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

    PubMed Central

    2012-01-01

    Background Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/L). Clinical stage (P = 0.004) and lymph node metastasis classification (P = 0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019). Conclusions Vitamin D deficiency may be associated with poor prognosis in gastric cancer. PMID:22284859

  10. Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications.

    PubMed

    Amin, Mahul B

    2009-06-01

    It is well established that invasive urothelial carcinoma, involving the urinary bladder and renal pelvis, has marked propensity for divergent differentiation. In recent years, several 'variant' morphologies have been described and most have been recognized in the 2004 World Health Organization Classification. These histological variants of urothelial carcinoma have clinical significance at various levels, including diagnostic, that is, awareness of the morphological variant is essential in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnostic assignment of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma. The diagnoses of micropapillary urothelial carcinoma, small-cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma are prime examples where treatment protocols may be different than the usual muscle-invasive bladder cancer. This review discusses the variants of urothelial carcinoma, outlining for each the diagnostic features, differential diagnostic considerations and the clinical significance.

  11. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

    PubMed Central

    Marsoni, S.; Torri, V.; Valsecchi, M. G.; Belloni, C.; Bianchi, U.; Bolis, G.; Bonazzi, C.; Colombo, N.; Epis, A.; Favalli, G.

    1990-01-01

    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed. PMID:2119684

  12. DEK: A novel early screening and prognostic marker for breast cancer.

    PubMed

    Ying, Guo; Wu, Yonghui

    2015-11-01

    The present study aimed to investigate the expression status and clinical implications of DEK in breast cancer, in order to contribute to developments in breast cancer management. DEK expression status was detected in 628 breast cancer specimens by western blot analysis and immunohistochemistry staining, and the correlation between DEK protein and clinico‑pathological parameters and prognosis of breast cancer was subsequently determined. In comparison to para-carcinoma tissues, DEK protein was highly expressed in breast cancer specimens and was correlated with chemotherapy resistance. In total, 61.94% (389/628) of breast cancer cases exhibited high expression of DEK. According to universal analysis, it was observed that age, tumor size, histological grade, metastatic nodes and distant metastasis (P=0.024, 0.001, 0.001, 0.001 and 0.001 respectively) are key factors associated with DEK. Furthermore, compared with samples with no or low DEK protein expression, high DEK expression resulted in a significantly increased distant metastasis rate and poor disease‑specific survival (P=0.001). In addition, DEK protein was detected as an independent prognostic factor (P=0.001) in the Cox regression analysis. DEK was correlated with chemotherapy resistance and may be an independent prognostic factor for breast cancer, as well as a potential therapeutic target.

  13. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    PubMed

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network.

  14. MicoRNA-425-5p is a potential prognostic biomarker for cervical cancer.

    PubMed

    Sun, Liwei; Jiang, Rong; Li, Jinduo; Wang, Bin; Ma, Chunhua; Lv, Yuan; Mu, Ning

    2017-01-01

    Background MicroRNAs have been implicated in many biological pathways involved in tumourigenesis and can serve as prognostic biomarkers in many cancer types. The present study aims at evaluating the prognostic significance of miR-425-5p in cervical cancer. Methods Real-time polymerase chain reaction was performed to assess the expression levels of miR-425-5p in 35 pairs of cervical cancer tissues and their matched normal tissues as well as serum samples from 40 cervical cancer patients, 13 benign cervical disease patients and 32 healthy controls. The association between miR-425-5p expression levels in tissue and serum, and clinicopathological factors was examined. The correlation between serum miR-425-5p expression levels and overall survival of cervical cancer patients was assessed by Kaplan-Meier analysis and Cox proportional hazards model. Results MiR-425-5p expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues. Higher expression of miR-425-5p was positively associated with high tumour stage ( P = 0.0003) and positive lymph node metastasis ( P = 0.0107). Serum concentrations of miR-425-5p in cervical cancer patients were significantly higher compared with benign cervical disease and healthy controls. Moreover, the up-regulation of serum miR-425-5p occurred more frequently in cervical cancer patients with high TNM stage ( P = 0.0003) and positive lymph node metastasis ( P = 0.0037). Kaplan-Meier analysis showed that high serum miR-425-5p expression levels predicted poor survival ( P = 0.0571). Cox proportional hazards risk analysis demonstrated that miR-425-5p was an independent prognostic factor for cervical cancer. Conclusion Our study suggests that miR-425-5p is up-regulated in cervical cancer and serum miR-425-5p may serve as a potential prognostic biomarker for cervical cancer.

  15. An evaluation of intelligent prognostic systems for colorectal cancer.

    PubMed

    Anand, S S; Smith, A E; Hamilton, P W; Anand, J S; Hughes, J G; Bartels, P H

    1999-02-01

    In this paper we describe attempts at building a robust model for predicting the length of survival of patients with colorectal cancer. The aim of the research, reported in this paper, is to study the effective utilisation of artificial intelligence techniques in the medical domain. We suggest that an important research objective of proponents of intelligent prognostic systems must be to evaluate the additionality that AI techniques can bring to an already well-established field of medical prognosis. Towards this end, we compare a number of different AI techniques that lend themselves to the task of predicting survival in colorectal cancer patients. We describe the pros and cons of each of these methods using the usual metrics of accuracy and perspicuity. We then present the notion of intelligent hybrid systems and evaluate the role that they may potentially play in developing robust prognostic models. In particular we evaluate a hybrid system that utilises the k Nearest Neighbour technique in conjunction with Genetic Algorithms. We describe a number of innovations used within this hybrid paradigm used to build the prognostic model. We discuss the issue of censored patients and how this issue can be tackled within the various models used. In keeping with our objective of studying the additionality that AI techniques bring to building prognostic models, we use Cox's regression as a standard and compare each AI technique with it, attempting to discover their capabilities in enhancing prognostic methods in medicine. In doing so we address two main questions--which model fits the data best?, and are the results obtained by the various AI techniques significantly different from those of Cox's regression? We conclude this paper by discussing future enhancements to the work presented and lessons learned from the study to date.

  16. Prognostic value of preoperative serum tumor markers in gastric cancer

    PubMed Central

    Huang, Ze-Bo; Zhou, Xin; Xu, Jun; Du, Yi-Ping; Zhu, Wei; Wang, Jian; Shu, Yong-Qian; Liu, Ping

    2014-01-01

    AIM: To evaluate the prognostic value of preoperative carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and CA50 in patients undergoing D2 resection. METHODS: We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9, and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses. RESULTS: The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and 24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age (P < 0.001), sex (P = 0.022), tumor size (P = 0.007) and depth of invasion (P = 0.018); CA19-9 with tumor size (P = 0.042) and lymph node metastasis (P < 0.001); and CA50 only with lymph node metastasis (P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy (P = 0.027). CONCLUSION: Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy. PMID:24829865

  17. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  18. Gender differences in prognostic factors for oral cancer.

    PubMed

    Honorato, J; Rebelo, M S; Dias, F L; Camisasca, D R; Faria, P A; Azevedo e Silva, G; Lourenço, S Q C

    2015-10-01

    The aim of this study was to assess gender differences in prognostic factors among patients treated surgically for oral squamous cell carcinoma (OSCC). The medical records of 477 eligible patients (345 males, 132 females) obtained from the Brazilian Cancer Institute were reviewed. Survival was calculated by Kaplan-Meier method. Cox regression models were used to obtain adjusted hazard ratios (aHR) for males and females. Multivariate analysis showed that past tobacco use (aHR 0.2, 95% confidence interval (CI) 0.1-0.7) and regional metastasis (aHR 2.3, 95% CI 1.5-3.5) in males, and regional metastasis (aHR 2.2, 95% CI 1.2-4.3), distant metastasis (aHR 6.7, 95% CI 1.3-32.7), and hard palate tumours (aHR 11.8, 95% CI 3.3-47.7) in females, were associated with a higher risk of death. There were no differences in survival between males and females. Regional metastasis was found to be a negative prognostic factor in OSCC for both genders. Past tobacco use was an independent prognostic factor for worse survival among males, while distant metastasis and hard palate tumours were independent prognostic factors for worse survival among females. Further studies are necessary to corroborate the relationships found in this study.

  19. Prognostic value of perioperative leukocyte count in resectable gastric cancer

    PubMed Central

    Chen, Xiao-Feng; Qian, Jing; Pei, Dong; Zhou, Chen; Røe, Oluf Dimitri; Zhu, Fang; He, Shao-Hua; Qian, Ying-Ying; Zhou, Yue; Xu, Jun; Xu, Jin; Li, Xiao; Ping, Guo-Qiang; Liu, Yi-Qian; Wang, Ping; Guo, Ren-Hua; Shu, Yong-Qian

    2016-01-01

    AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer. METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors. RESULTS: The mean white blood cell count (WBC) significantly decreased after surgery, and 107/614 (17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio (HR) = 1.602, 95% confidence interval (CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, pTNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p-leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia (27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer. PMID:26973420

  20. Prognostic value of circulating tumor cells in esophageal cancer

    PubMed Central

    Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

    2017-01-01

    AIM 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. METHODS 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. RESULTS 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. CONCLUSION 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. PMID:28275311

  1. Pulmonary Hypertension in Heart Failure Patients: Pathophysiology and Prognostic Implications.

    PubMed

    Guazzi, Marco; Labate, Valentina

    2016-12-01

    Pulmonary hypertension (PH) due to left heart disease (LHD), i.e., group 2 PH, is the most common reason for increased pressures in the pulmonary circuit. Although recent guidelines incorporate congenital heart disease in this classification, left-sided heart diseases of diastolic and systolic origin including valvular etiology are the vast majority. In these patients, an increased left-sided filling pressure triggers a multistage hemodynamic evolution that ends into right ventricular failure through an initial passive increase in pulmonary artery pressure complicated over time by pulmonary vasoconstriction, endothelial dysfunction, and remodeling of the small-resistance pulmonary arteries. Regardless of the underlying left heart pathology, when present, PH-LHD is associated with more severe symptoms, worse exercise tolerance, and outcome, especially when right ventricular dysfunction and failure are part of the picture. Compared with group 1 and other forms of pulmonary arterial hypertension, PH-LHD is more often seen in elderly patients with a higher prevalence of cardiovascular comorbidities and most, if not all, of the features of metabolic syndrome, especially in case of HF preserved ejection fraction. In this review, we provide an update on current knowledge and some potential challenges about the pathophysiology and established prognostic implications of group 2 PH in patients with HF of either preserved or reduced ejection fraction.

  2. Clinicopathological classification and traditional prognostic indicators of breast cancer

    PubMed Central

    Li, Jiehua; Chen, Zhibai; Su, Ka; Zeng, Jian

    2015-01-01

    Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. The objective of this study is to evaluate the value of molecular subtypes in breast cancer management according to a retrospective analysis of breast carcinoma molecular subtypes, histopathological grade, and TNM stage. A retrospective study of 475 paraffin-embedded tissues of breast cancer samples from the First Affiliated Hospital of Guangxi Medical University was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The differences of molecular subtypes of breast cancers in regard to TNM staging and pathological grade were analyzed using χ2 tests. Values of P<0.05 were considered statistically significant. The frequency of luminal A, luminal B, HER2-positive luminal B, triple negative and non-luminal HER2-positive subtypes were: 35.5%, 22.5%, 13.1%, 15.2% and 13.7%, respectively. Among the five subtypes of breast cancer, the distribution of pathological grades showed a significant difference (P<0.001). There were significant differences in the distribution of TNM staging among the five subtypes of breast cancer (P<0.001). In addition to traditional prognostic indicators such as TNM staging and pathological grade, molecular subtype may aid clinical practice and research into breast cancer. Different molecular subtypes will lead to different prognosis and therapeutic option. Molecular subtyping is essential for breast cancer management. PMID:26339424

  3. Prognostic relevance of minimal residual disease in colorectal cancer

    PubMed Central

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-01-01

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID:25132746

  4. Prognostic significance of selected lifestyle factors in urinary bladder cancer.

    PubMed

    Wakai, K; Ohno, Y; Obata, K; Aoki, K

    1993-12-01

    To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

  5. Prognostic significance of KLF4 expression in gastric cancer

    PubMed Central

    Hashimoto, Isaya; Nagata, Takuya; Sekine, Shinichi; Moriyama, Makoto; Shibuya, Kazuto; Hojo, Shozo; Matsui, Koshi; Yoshioka, Isaku; Okumura, Tomoyuki; Hori, Takashi; Shimada, Yutaka; Tsukada, Kazuhiro

    2017-01-01

    To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. PMID:28356964

  6. Prognostic factors and survival in patients with gastric stump cancer

    PubMed Central

    Huang, Hua; Wang, Wei; Chen, Zhong; Jin, Jie-Jie; Long, Zi-Wen; Cai, Hong; Liu, Xiao-Wen; Zhou, Ye; Wang, Ya-Nong

    2015-01-01

    AIM: To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer (GSC). METHODS: The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center. The prognostic factors were analyzed with Cox proportional hazard models. RESULTS: GSC tended to occur within 25 years following the primary surgery, when the initial disease is benign, whereas it primarily occurred within the first 15 years post-operation for gastric cancer. Patients with regular follow-up after primary surgery had a better survival rate. The multivariate Cox regression analysis revealed that Borrmann type I/II (HR = 3.165, 95%CI: 1.055-9.500, P = 0.040) and radical resection (HR = 1.780, 95%CI: 1.061-2.987, P = 0.029) were independent prognostic factors for GSC. The overall 1-, 3-, and 5-year survival rates of the 92 patients were 78.3%, 45.6% and 27.6%, respectively. The 1-, 3-, and 5-year survival rates of those undergoing radical resection were 79.3%, 52.2%, and 37.8%, respectively. The 5-year survival rates for stages I, II, III, and IV were 85.7%, 47.4%, 16.0%, and 13.3%, respectively (P = 0.005). CONCLUSION: The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease. Therefore, close follow-up is necessary. The overall survival of patients with GSC is poor, and curative resection can improve their prognosis. PMID:25684953

  7. Prognostic factors in early-stage ovarian cancer

    PubMed Central

    Tognon, Germana; Carnazza, Mario; Ragnoli, Monica; Calza, Stefano; Ferrari, Federico; Gambino, Angela; Zizioli, Valentina; Notaro, Sara; Sostegni, Benedetta; Sartori, Enrico

    2013-01-01

    The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I–IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20–250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1–G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino. PMID:23781280

  8. EGFR genomic alterations in cancer: prognostic and predictive values.

    PubMed

    Bronte, Giuseppe; Terrasi, Marianna; Rizzo, Sergio; Sivestris, Nicola; Ficorella, Corrado; Cajozzo, Massimo; Di Gaudio, Francesca; Gulotta, Gaspare; Siragusa, Sergio; Gebbia, Nicola; Russo, Antonio

    2011-06-01

    The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy number, are currently under investigation. This review summarizes both preclinical and clinical available data regarding EGFR genomic alterations as prognostic and predictive factors.

  9. Prognostic implications of Kindlin proteins in human osteosarcoma

    PubMed Central

    Ning, Kai; Zhang, Haoshaqiang; Wang, Zhigang; Li, Kun

    2017-01-01

    The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both P<0.01), but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<0.05), than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both P=0.01), presence of metastasis (both P=0.006), recurrence (both P=0.006) and poor response to chemotherapy (both P=0.02). Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01) and disease-free (P=0.02 and 0.01, respectively) survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients’ prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function as reliable markers for progression and prognosis in osteosarcoma patients, especially for tumor recurrence. PMID:28223823

  10. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  11. Prognostic significance of PLIN1 expression in human breast cancer

    PubMed Central

    Zhou, Cefan; Wang, Ming; Zhou, Li; Zhang, Yi; Liu, Weiyong; Qin, Wenying; He, Rong; Lu, Yang; Wang, Yefu; Chen, Xing-Zhen; Tang, Jingfeng

    2016-01-01

    Breast cancer is a heterogeneous disease associated with diverse clinical, biological and molecular features, presenting huge challenges for prognosis and treatment. Here we found that perilipin-1 (PLIN1) mRNA expression is significantly downregulated in human breast cancer. Kaplan-Meier analysis indicated that patients presenting with reduced PLIN1 expression exhibited poorer overall metastatic relapse-free survival (p = 0.03). Further Cox proportional hazard models analysis revealed that the reduced expression of PLIN1 is an independent predictor of overall survival in estrogen receptor positive (p < 0.0001, HR = 0.87, 95% CI = 0.81–0.92, N = 3,600) and luminal A-subtype (p = 0.02, HR = 0.88, 95% CI = 0.78–0.98, N = 1,469) breast cancer patients. We also demonstrated that the exogenous expression of PLIN1 in human breast cancer MCF-7 and MDA-MB-231 cells significantly inhibits cell proliferation, migration, invasion and in vivo tumorigenesis in mice. Together, these data provide novel insights into a prognostic significance of PLIN1 in human breast cancer and reveal a potentially new gene therapy target for breast cancer. PMID:27359054

  12. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  13. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Jammal, Millena Prata; Martins-Filho, Agrimaldo; Silveira, Thales Parenti; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2016-01-01

    INTRODUCTION Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors. METHOD The study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05. RESULTS TNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently. CONCLUSION IL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies. PMID:27512342

  14. Nuclear osteopontin-c is a prognostic breast cancer marker

    PubMed Central

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-01-01

    Background: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Methods: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. Results: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. Conclusions: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis. PMID:25625274

  15. The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target

    PubMed Central

    Di Martile, Marta; Del Bufalo, Donatella; Trisciuoglio, Daniela

    2016-01-01

    Lysine acetylation is a post-translational modification that regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. Recently, several reports have demonstrated that numerous cytosolic proteins are also acetylated and that this modification, affecting protein activity, localization and stability has profound consequences on their cellular functions. Interestingly, most non-histone proteins targeted by acetylation are relevant for tumorigenesis. In this review, we will analyze the functional implications of lysine acetylation in different cellular compartments, and will examine our current understanding of lysine acetyltransferases family, highlighting the biological role and prognostic value of these enzymes and their substrates in cancer. The latter part of the article will address challenges and current status of molecules targeting lysine acetyltransferase enzymes in cancer therapy. PMID:27322556

  16. Pathological significance and prognostic implications of heme oxygenase 1 expression in non-muscle-invasive bladder cancer: Correlation with cell proliferation, angiogenesis, lymphangiogenesis and expression of VEGFs and COX-2

    PubMed Central

    Matsuo, Tomohiro; Miyata, Yasuyoshi; Mitsunari, Kensuke; Yasuda, Takuji; Ohba, Kojiro; Sakai, Hideki

    2017-01-01

    Heme oxygenase 1 (HO-1) is a stress-response protein and its expression is associated with malignant potential and poor prognosis in several types of cancer. The present study investigated the association between HO-1 expression levels and the pathological features, clinical outcomes and other associated factors in patients with non-muscle-invasive bladder cancer (NMIBC). HO-1 expression was evaluated using immunohistochemistry in 147 formalin-fixed tissue specimens. The proliferation index, microvessel density, lymph vessel density and expression of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D were also investigated. Correlations among variables were analyzed by multivariate analysis. Survival was assessed using Kaplan-Meier survival curves and multivariate statistics. HO-1 expression levels in high-grade and pT1 tumors were significantly higher compared with low-grade and pTa tumors, and were correlated with the proliferation index (P<0.001), lymph vessel density (P=0.021) and COX-2 expression levels (P=0.003). The proliferation index and COX-2 expression levels were also identified as independent contributing factors in multivariate models. Kaplan-Meier survival curves associated HO-1 expression with a poor prognosis in metastasis-free (P=0.047) and cause-specific survival (P=0.017), but not with urinary tract recurrence (P=0.231). Furthermore, HO-1 expression was identified by multivariate analysis to be a significant predictor for cause-specific survival (hazard ratio, 4.08; 95% confidence interval, 1.06–15.66; P=0.004). HO-1 has an important role in the malignant aggressiveness of NMIBC and its expression is associated with cause-specific survival. HO-1-associated activities are regulated by cancer cell proliferation, lymphangiogenesis and COX-2. The results suggest that HO-1 may be a potential therapeutic target and a useful predictive prognostic factor in patients with NMIBC. PMID:28123555

  17. A Prognostic Model for Patients with Triple-Negative Breast Cancer: Importance of the Modified Nottingham Prognostic Index and Age

    PubMed Central

    Kwon, Jeanny; Eom, Keun-Yong; Koo, Tae Ryool; Kim, Byoung Hyuck; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Park, So Yeon

    2017-01-01

    Purpose Considering the distinctive biology of triple-negative breast cancer (TNBC), this study aimed to identify TNBC-specific prognostic factors and determine the prognostic value of the Nottingham Prognostic Index (NPI) and its variant indices. Methods A total of 233 patients with newly diagnosed stage I to III TNBC from 2003 to 2012 were reviewed. We retrospectively analyzed the patients' demographics, clinicopathologic parameters, treatment, and survival outcomes. The NPI was calculated as follows: tumor size (cm)×0.2+node status+Scarff-Bloom-Richardson (SBR) grade. The modified NPI (MNPI) was obtained by adding the modified SBR grade rather than the SBR grade. Results The median follow-up was 67.8 months. Five-year disease-free survival (DFS) and overall survival (OS) were 81.4% and 89.9%, respectively. Multivariate analyses showed that the MNPI was the most significant and common prognostic factor of DFS (p=0.001) and OS (p=0.019). Young age (≤35 years) was also correlated with poor DFS (p=0.006). A recursive partitioning for establishing the prognostic model for DFS was performed based on the results of multivariate analysis. Patients with a low MNPI (≤6.5) were stratified into the low-risk group (p<0.001), and patients with a high MNPI (>6.5) were subdivided into the intermediate (>35 years) and high-risk (≤35 years) groups. Age was not a prognostic factor in patients with a low MNPI, whereas in patients with a high MNPI, it was the second key factor in subdividing patients according to prognosis (p=0.023). Conclusion The MNPI could be used to stratify patients with stage I to III TNBC according to prognosis. It was the most important prognosticator for both DFS and OS. The prognostic significance of young age for DFS differed by MNPI. PMID:28382096

  18. Prognostic value of glycated hemoglobin in colorectal cancer

    PubMed Central

    Ferroni, Patrizia; Formica, Vincenzo; Della-Morte, David; Lucchetti, Jessica; Spila, Antonella; D'Alessandro, Roberta; Riondino, Silvia; Guadagni, Fiorella; Roselli, Mario

    2016-01-01

    AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients. METHODS Pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated. RESULTS Fasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients. CONCLUSION HbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes. PMID:28018105

  19. Reproducibility of residual cancer burden for prognostic assessment of breast cancer after neoadjuvant chemotherapy.

    PubMed

    Peintinger, Florentia; Sinn, Bruno; Hatzis, Christos; Albarracin, Constance; Downs-Kelly, Erinn; Morkowski, Jerzy; Gould, Rebekah; Symmans, W Fraser

    2015-07-01

    The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden

  20. Prognostic value of a 92-probe signature in breast cancer.

    PubMed

    Akter, Salima; Choi, Tae Gyu; Nguyen, Minh Nam; Matondo, Abel; Kim, Jin-Hwan; Jo, Yong Hwa; Jo, Ara; Shahid, Muhammad; Jun, Dae Young; Yoo, Ji Youn; Nguyen, Ngoc Ngo Yen; Seo, Seong-Wook; Ali, Liaquat; Lee, Ju-Seog; Yoon, Kyung-Sik; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Jayoung; Kim, Sung Soo

    2015-06-20

    Clinical applications of gene expression signatures in breast cancer prognosis still remain limited due to poor predictive strength of single training datasets and appropriate invariable platforms. We proposed a gene expression signature by reducing baseline differences and analyzing common probes among three recent Affymetrix U133 plus 2 microarray data sets. Using a newly developed supervised method, a 92-probe signature found in this study was associated with overall survival. It was robustly validated in four independent data sets and then repeated on three subgroups by incorporating 17 breast cancer microarray datasets. The signature was an independent predictor of patients' survival in univariate analysis [(HR) 1.927, 95% CI (1.237-3.002); p < 0.01] as well as multivariate analysis after adjustment of clinical variables [(HR) 7.125, 95% CI (2.462-20.618); p < 0.001]. Consistent predictive performance was found in different multivariate models in increased patient population (p = 0.002). The survival signature predicted a late metastatic feature through 5-year disease free survival (p = 0.006). We identified subtypes within the lymph node positive (p < 0.001) and ER positive (p = 0.01) patients that best reflected the invasive breast cancer biology. In conclusion using the Common Probe Approach, we present a novel prognostic signature as a predictor in breast cancer late recurrences.

  1. Immunohistochemical prognostic index for breast cancer in young women

    PubMed Central

    Guerra, I; Algorta, J; Díaz de Otazu, R; Pelayo, A; Fariña, J

    2003-01-01

    Aims: Women under 35 years of age comprise a small proportion of patients with breast cancer, but determining their prognosis can be difficult. This prospective, multivariate study looked at several factors with the aim of obtaining a useful index to evaluate the prognosis of these women. Methods: In total, 108 patients below 35 years of age affected by invasive ductal carcinoma without distant metastasis were studied. The mean duration of the follow up period was six years. Histopathological (tumour size, histological grade, and lymph node stage) and immunohistochemical (c-erbB-2, p53, oestrogen receptor, and progesterone receptor) factors were measured in all patients, and the Nottingham prognostic index (NPI) was then calculated. An immunohistochemical prognostic index (IHPI) was created using the arithmetic sum of the four individual immunohistochemical factors. Results: In univariate assessment of survival, all the studied factors yielded a significant association with either overall survival or disease free survival, except for c-erbB-2 and p53 with disease free survival. In univariate calculation of risk, all the factors gave significant results; however, in multivariate analysis only tumour size, histological grade, and progesterone receptor were significant. Both NPI and IHPI correlated significantly with prognosis. In multivariate regression analysis, IHPI correlated with tumour size and there was a significant interaction between both variables. Conclusion: IHPI is very useful in determining the prognosis of tumours ⩽ 2 cm and of moderate use for tumours > 2, although it has no use in tumours > 5 cm. PMID:14645694

  2. Expression and prognostic significance of apolipoprotein D in breast cancer.

    PubMed Central

    Díez-Itza, I.; Vizoso, F.; Merino, A. M.; Sánchez, L. M.; Tolivia, J.; Fernández, J.; Ruibal, A.; López-Otín, C.

    1994-01-01

    Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death. Images Figure 1 Figure 2 Figure 3 PMID:8311115

  3. Expression of FGFR1 is an independent prognostic factor in triple-negative breast cancer.

    PubMed

    Cheng, Chee Leong; Thike, Aye Aye; Tan, Sie Yong Jane; Chua, Pei Jou; Bay, Boon Huat; Tan, Puay Hoon

    2015-05-01

    Triple-negative breast cancers (TNBCs) are clinically aggressive tumors with limited treatment options. We examined the clinicopathological associations and prognostic implications of FGFR1 and FGFR2 expression in TNBCs. Tissue microarrays constructed from TNBCs were immunostained with FGFR1 and FGFR2, and scored by intensity and percentage of tumor cells stained per intensity for each subcellular compartment, which were correlated with clinicopathological parameters and survival. Cell migration following siRNA-mediated silencing of the FGFR1 gene in TNBC cell lines was also performed. 714 cases were informative for FGFR1 and FGFR2 immunostaining. Thresholds were defined as at least 1 % of cells stained and H-score of 100 or more. Proportions positive by each threshold were, respectively, 89.9 %, 7.1 % for FGFR1 (cytoplasm); 36.8 %, 7.8 % for FGFR2 (cytoplasm); and 33.5 %, 5.2 % for FGFR2 (membrane). Significant associations included FGFR1 and FGFR2 immunostaining for lobular subtype, FGFR2 immunostaining with lower grade, and more basal-like cancers with H-scores of 100 or more FGFR1 immunostaining. Multivariate Cox regression analysis showed FGFR1 expression in TNBCs to be independently prognostic for overall survival (OS) at both thresholds. Cases completely negative (less than 1 % staining) for FGFR1 immunostaining showed improved OS, while those with H-score of 100 or more immunostaining had the worst OS. Cell line studies revealed up-regulation of the FGFR1 gene in the MDA-MB-231 and Hs578T TNBC cells, and specific knockdown of FGFR1 expression significantly reduced cell migration in MDA-MB-231 cell line. In conclusion, FGFR1 expression in TNBCs is independently prognostic of OS, and H-score of 100 or more FGFR1 immunostaining may define tumors that have treatment potential via FGFR signaling inhibition.

  4. Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer

    PubMed Central

    Pan, Xin; Cai, Lu; Lin, Xiao-Yan; Chen, Su; Biskup, Ewelina

    2016-01-01

    Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator–activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis. PMID:27780920

  5. Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer.

    PubMed

    Cai, Feng-Feng; Xu, Cheng; Pan, Xin; Cai, Lu; Lin, Xiao-Yan; Chen, Su; Biskup, Ewelina

    2016-11-22

    Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator-activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.

  6. Prognostic value of innate and adaptive immunity in colorectal cancer.

    PubMed

    Grizzi, Fabio; Bianchi, Paolo; Malesci, Alberto; Laghi, Luigi

    2013-01-14

    Colorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit.

  7. Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

    PubMed Central

    Han, Wonshik; Kim, Jongjin; Moon, Hyeong-Gon; Oh, Sohee; Song, Yun Seon; Kim, Young A; Chang, Mee Soo; Noh, Dong-Young

    2017-01-01

    Purpose We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. Methods We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(–) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(–)/HER2(+) and HR(–)/HER2(–) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(–) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(–), HR(+)/HER2(+), and HR(–)/HER2(–) subtypes, but not in HR(–)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. Conclusion The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(–) or luminal A and luminal B/HER2(–) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2. PMID:28382095

  8. A generic cycling hypoxia-derived prognostic gene signature: application to breast cancer profiling

    PubMed Central

    Helleputte, Thibault; Rubio, Laila Illan; Dupont, Pierre; Feron, Olivier

    2014-01-01

    Background Temporal and local fluctuations in O2 in tumors require adaptive mechanisms to support cancer cell survival and proliferation. The transcriptome associated with cycling hypoxia (CycHyp) could thus represent a prognostic biomarker of cancer progression. Methods We exposed 20 tumor cell lines to repeated periods of hypoxia/reoxygenation to determine a transcriptomic CycHyp signature and used clinical data sets from 2,150 breast cancer patients to estimate a prognostic Cox proportional hazard model to assess its prognostic performance. Results The CycHyp prognostic potential was validated in patients independently of the receptor status of the tumors. The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations including those with a node negative status under treatment (HR=3.16) or not (HR=5.54). The CycHyp prognostic signature outperformed a signature derived from continuous hypoxia and major prognostic metagenes (P<0.001). The CycHyp signature could also identify ER+HER2 node-negative breast cancer patients at high risk based on clinicopathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based but who presented a negative outcome. Conclusions The CycHyp signature is prognostic of breast cancer and offers a unique decision making tool to complement anatomopathologic evaluation. PMID:25216520

  9. Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

    PubMed

    González García, A; Patier de la Peña, J L; Ortego Centeno, N

    2017-03-01

    Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults.

  10. Reproducibility of Residual Cancer Burden For Prognostic Assessment of Breast Cancer After Neoadjuvant Chemotherapy

    PubMed Central

    Peintinger, Florentia; Sinn, Bruno; Hatzis, Christos; Albarracin, Constance; Downs-Kelly, Erinn; Morkowski, Jerzy; Gould, Rebekah; Symmans, W. Fraser

    2016-01-01

    The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports from 100 cases selected at random from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists at M.D Anderson Cancer Center without prior coaching. Size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were evaluated and analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among all five pathologists was 0.931 (95% Confidence Interval 0.908 – 0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% Confidence Interval 0.539 – 0.626), indicating good overall inter-pathologist agreement. The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient = 0.980; 95% Confidence Interval 0.954 – 0.992), than the primary component (overall concordance correlation coefficient = 0.795; 95% Confidence Interval 0.716 – 0.853). At a median follow-up of 12 years residual cancer burden

  11. Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

    PubMed Central

    Bovenzi, Cory D.; Hamilton, James; Tassone, Patrick; Johnson, Jennifer; Cognetti, David M.; Luginbuhl, Adam; Keane, William M.; Zhan, Tingting; Tuluc, Madalina; Bar-Ad, Voichita; Martinez-Outschoorn, Ubaldo; Curry, Joseph M.

    2015-01-01

    Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations. PMID:26779534

  12. Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

    PubMed Central

    Xia, Pu; Xu, Xiao-Yan

    2016-01-01

    CD44 is a well-recognized stem cell biomarker expressed in colon and gastric cancer. In order to identify whether CD44 mRNA could be used as a prognostic marker in colon and gastric cancer, bioinformatic analyses were used in this study. cBioPortal analysis and COSMIC analysis were used to explore the CD44 mutation. CD44 mRNA levels were evaluated by using SAGE Genie tools and Oncomine analysis. Kaplan-Meier Plotter was performed to identify the prognostic roles of CD44 mRNA in these two cancers. In this study, first, we found that low alteration frequency of CD44 mRNA in colon and gastric cancer. Second, the high CD44 mRNA level was found in colon and gastric cancer, and it correlated with a benign survival rate in gastric cancer. Third, CD4 and CD74 may be used as markers to predict the prognosis of colon and gastric cancer. However, the deep mechanism(s) of these results remains unclear, further studies have to be performed in the future. PMID:27323782

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

    SciTech Connect

    Niwinska, Anna; 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 2.4 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.

  14. The prognostic roles of ALDH1 isoenzymes in gastric cancer

    PubMed Central

    Li, Kai; Guo, Xiaoguang; Wang, Ziwei; Li, Xiaofeng; Bu, Youquan; Bai, Xuefeng; Zheng, Liansheng; Huang, Ying

    2016-01-01

    Increased aldehyde dehydrogenase 1 (ALDH1) activity has been determined to be present in the stem cells of several kinds of cancers including gastric cancer (GC). Nevertheless, which ones of ALDH1’s isoenzymes are leading to ALDH1 activity remains elusive. In this study, we examined the prognostic value and hazard ratio (HR) of individual ALDH1 isoenzymes in patients with GC using “The Kaplan–Meier plotter” database. mRNA high expression level of ALDH1A1 was not found to be significantly correlated with the overall survival (OS) of all patients with GC followed for 20 years, HR =0.86 (95% confidence interval [CI]: 0.7–1.05), P=0.13. mRNA high expression level of ALDH1A2 was also not significantly correlated with OS for all patients with GC, HR =1.13 (95% CI: 0.91–1.41), P=0.25. mRNA high expression level of ALDH1A3 was found to be significantly correlated with worsened OS in either intestinal-type patients, HR =2.24 (95% CI: 1.44–3.49), P=0.00026, or diffuse-type patients, HR =1.91 (95% CI: 1.02–3.59), P=0.04. Interestingly, mRNA high expression level of ALDH1B1 was found to be significantly correlated with better OS for all patients with GC, HR =0.66 (95% CI: 0.53–0.81), P=7.8e–05, and mRNA high expression level of ALDH1L1 was found to be significantly correlated with worsened OS for all patients with GC, HR =1.23 (95% CI: 1–1.51), P=0.048. Furthermore, our results also indicate that ALDH1A3 and ALDH1L1 are potential major contributors to the ALDH1 activity in GC, since mRNA high expression levels of ALDH1A3 and ALDH1L1 were found to be significantly correlated with worsened OS for all patients with GC. Based on our study, ALDH1A3 and ALDH1L1 are potential prognostic markers and therapeutic targets for patients with GC. PMID:27354812

  15. Tumor Volume Reduction Rate during Adaptive Radiation Therapy as a Prognosticator for Nasopharyngeal Cancer

    PubMed Central

    Lee, Hyebin; Ahn, Yong Chan; Oh, Dongryul; Nam, Heerim; Noh, Jae Myoung; Park, Su Yeon

    2016-01-01

    Purpose The purpose of this study is to evaluate the prognostic significance of the tumor volume reduction rate (TVRR) measured during adaptive definitive radiation therapy (RT) for nasopharyngeal cancer (NPC). Materials and Methods We reviewed the RT records of 159 NPC patients treated with definitive RT with or without concurrent chemotherapy between January 2006 and February 2013. Adaptive re-planning was performed in all patients at the third week of RT. The pre- and mid-RT gross tumor volumes (GTVs) of the primary tumor and the metastatic lymph nodes were measured and analyzed for prognostic implications. Results After a median follow-up period of 41.5 months (range, 11.2 to 91.8 months) for survivors, there were 43 treatment failures. The overall survival and progression-free survival (PFS) rates at 5 years were 89.6% and 69.7%, respectively. The mean pre-RT GTV, mid-RT GTV, and TVRR were 45.9 cm3 (range, 1.5 to 185.3 cm3), 26.7 cm3 (1.0 to 113.8 cm3), and –41.9% (range, –87% to 78%), respectively. Patients without recurrence had higher TVRR than those with recurrence (44.3% in the no recurrence group vs. 34.0% in the recurrence group, p=0.004), and those with TVRR > 35% achieved a significantly higher rate of PFS at 5 years (79.2% in TVRR > 35% vs. 53.2% in TVRR ≤ 35%; p < 0.001). In multivariate analysis, TVRR was a significant factor affecting PFS (hazard ratio, 2.877; 95% confidence interval, 1.555 to 5.326; p=0.001). Conclusion TVRR proved to be a significant prognostic factor in NPC patients treated with definitive RT, and could be used as a potential indicator for early therapeutic modification during the RT course. PMID:26194371

  16. Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa).

    PubMed

    Nuzzo, Pier Vitale; Rubagotti, Alessandra; Argellati, Francesca; Di Meglio, Antonio; Zanardi, Elisa; Zinoli, Linda; Comite, Paola; Mussap, Michele; Boccardo, Francesco

    2015-07-28

    PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

  17. Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa)

    PubMed Central

    Nuzzo, Pier Vitale; Rubagotti, Alessandra; Argellati, Francesca; Di Meglio, Antonio; Zanardi, Elisa; Zinoli, Linda; Comite, Paola; Mussap, Michele; Boccardo, Francesco

    2015-01-01

    PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients. PMID:26225965

  18. Prognostic value of hedgehog signaling pathway in patients with colon cancer.

    PubMed

    Xu, Meihua; Li, Xinhua; Liu, Ting; Leng, Aimin; Zhang, Guiying

    2012-06-01

    Hedgehog signaling pathway plays an important role in normal mammalian gastrointestinal development and is implicated in the oncogenesis of various tumors. However, its correlation with progression and prognosis of colon cancer has not been well documented. This study was designed to investigate expression patterns of related proteins in hedgehog signaling pathway in colon cancer to elucidate its prognostic value in this tumor. Using human colon cancer and their corresponding non-diseased colon from 228 patients' biopsies, the expression of sonic hedgehog, its receptor Patched, and downstream transcription factor Gli1 was investigated by immunohistochemical staining to assess their association with the clinicopathological characteristics of colon cancer. Disease-free survival and overall survival were examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox analysis. One hundred and thirty-eight patients (59.6%) had sonic hedgehog-positive tumors and that the disease-free survival (43.5 vs. 73.3%, P < 0.001), and overall survival rates (50.7 vs. 88.9%, P < 0.001) of patients with sonic hedgehog-positive tumors were much lower than those of patients with sonic hedgehog-negative tumors. In addition, 163 patients (71.5%) had Patched-positive tumors, and the disease-free survival (41.7 vs. 76.9%, P < 0.001) and overall survival rates (55.2 vs. 80.0%, P = 0.002) of patients with Patched-positive tumors were also lower than those of patients with Patched-negative tumors. Moreover, positive Gli1 expression had a bad effect on the disease-free survival (41.9 vs. 73.2%, P < 0.001) and overall survival rate of patients with colon cancer (50.0 vs. 89.3%, P < 0.001). In a multivariate analysis, sonic hedgehog, Patched, and Gli1 status were indicators for poor disease-free survival and overall survival. These results have shown that the increasing expression of sonic hedgehog, Patched, and Gli1 are indicators for a poor

  19. Diagnostic and Prognostic Markers in Differentiated Thyroid Cancer

    PubMed Central

    Gómez Sáez, José M

    2011-01-01

    The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumor suppressor and thyroid-specific genes is associated with tumor aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. In the present manuscript the currently developed diagnostic and prognostic genetic/epigenetic markers are presented; the understanding of this molecular mechanism provides access to novel molecular therapeutic strategies. PMID:22654559

  20. Family history in breast cancer is not a prognostic factor?

    PubMed

    Jobsen, J J; Meerwaldt, J H; van der Palen, J

    2000-04-01

    The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 < or =3 cm were treated. Family history (FH) was recorded according to first degree relative (FDR). Treatment consisted of lumpectomy with axillary dissection followed by radiotherapy to the whole breast with a boost to the primary area. Adjuvant systemic therapy was given to patients with positive nodes. A positive FH was noted in 243 (20.5%) patients, of whom 208 (17.6%) had one FDR, and 35 (3.0%) > or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, < or =40 years, a significant relation between local recurrence and FH was found. The distant metastasis rate was 15.5%, with the lowest rate (5.7%) among patients with > or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years.

  1. Head and neck sarcomas: prognostic factors and implications for treatment.

    PubMed Central

    Eeles, R. A.; Fisher, C.; A'Hern, R. P.; Robinson, M.; Rhys-Evans, P.; Henk, J. M.; Archer, D.; Harmer, C. L.

    1993-01-01

    One hundred and thirty patients with soft tissue sarcoma of the head and neck were treated at the Royal Marsden Hospital between 1944 and 1988. Pathological review was possible in 103 of these cases; only pathologically reviewed cases have been analysed. The median age at presentation was 36 years, and 53% were male. Four had neurofibromatosis type I, and one previous bilateral retinoblastoma. Six had undergone previous radiotherapy, 12 to 45 years prior to developing sarcoma. The tumours were < or = 5 cm in 78% of cases and high grade in 48%. Only one patient presented with lymph node metastases and only one with distant metastases (to lung). Malignant fibrous histiocytoma was the commonest histological type, occurring in 30 cases. The overall 5 year survival was 50% (95% CI 39-60). Local tumour was the cause of death in 63% of cases and 5 year local control was only 47% (95% CI 36-58) with local recurrence occurring as late as 15 years after treatment. The only favourable independent prognostic factor for survival was the ability to perform surgery (other than biopsy), with or without radiotherapy, as opposed to radiotherapy alone (hazard ratio 0.39; P = 0.003). Only one patient had a biopsy with no further treatment. Favourable independent prognostic factors for local control at 5 years were site (tumours of the head as opposed to the neck, hazard ratio 0.42; P = 0.02) and modality of treatment (combined surgery and radiotherapy compared to either alone, hazard ratio 0.31; P = 0.002). Patients in the combined modality and single treatment modality groups were well balanced for T stage, grade and tumour site. The patients in the combined treatment group had less extensive surgery, yet their local recurrence-free survival was longer. Unlike soft tissue sarcomas at other sites, those in the head and neck region more often cause death by local recurrence. The addition of radiotherapy to surgery may result in longer local recurrence-free survival. PMID:8318414

  2. Expression of tNASP in Prostate Cancer: Opportunities for a Novel Diagnostic and Prognostic Biomarker Development

    DTIC Science & Technology

    2013-12-01

    Cancer : Opportunities for a Novel Diagnostic and Prognostic Biomarker Development PRINCIPAL INVESTIGATOR: Oleg M. Alekseev CONTRACTING...Expression of tNASP in Prostate Cancer : Opportunities for a Novel Diagnostic and Prognostic Biomarker Development 5a. CONTRACT NUMBER...Expression of tNASP in Prostate Cancer : Opportunities for a Novel Diagnostic and Prognostic Biomarker Development 5b. GRANT NUMBER W81XWH-12-1-0361

  3. Prognostic implications of normal exercise thallium 201 images

    SciTech Connect

    Wahl, J.M.; Hakki, A.H.; Iskandrian, A.S.

    1985-02-01

    A study was made of 455 patients (mean age, 51 years) in whom exercise thallium 201 scintigrams performed for suspected coronary artery disease were normal. Of those, 322 (71%) had typical or atypical angina pectoris and 68% achieved 85% or more maximal predicted heart rate. The exercise ECGs were abnormal in 68 patients (15%), normal in 229 (50%), and inconclusive in 158 (35%). Ventricular arrhythmias occurred during exercise in 194 patients (43%). After a mean follow-up period of 14 months, four patients had had cardiac events, sudden cardiac death in one and nonfatal myocardial infarctions in three. None of the four patients had abnormal exercise ECGs. Two had typical and two had atypical angina pectoris. Normal exercise thallium 201 images identify patients at a low risk for future cardiac events (0.8% per year), patients with abnormal exercise ECGs but normal thallium images have good prognoses, and exercise thallium 201 imaging is a better prognostic predictor than treadmill exercise testing alone, because of the high incidence of inconclusive exercise ECGs and the good prognosis in patients with abnormal exercise ECGs.

  4. Phosphorylation: Implications in Cancer.

    PubMed

    Singh, Vishakha; Ram, Mahendra; Kumar, Rajesh; Prasad, Raju; Roy, Birendra Kumar; Singh, Kaushal Kumar

    2017-02-01

    Post translational modifications (PTMs) are involved in variety of cellular activities and phosphorylation is one of the most extensively studied PTM, which regulates a number of cellular functions like cell growth, differentiation, apoptosis and cell signaling in healthy condition. However, alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers. Tyrosine kinase family encompasses the greatest number of oncoproteins. MAPK cascade has an importance role in cancer growth and progression. Bcl-2 family proteins serve either proapoptotic or antiapoptotic function. Cadherin-catenin complex regulates cell adhesion properties and cyclins are the key regulators of cell cycle. Altered phosphorylations in any of the above pathways are strongly associated with cancer, at the same time they serve as the potential tergets for drug development against cancer. Drugs targeting tyrosine kinase are potent anticancer drugs. Inhibitors of MEK, PI3K and ERK signalling pathways are undergoing clinical trials. Thus, drugs targeting phosphorylation pathways represent a promising area for cancer therapy.

  5. Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer

    PubMed Central

    Enzinger, Andrea C.; Zhang, Baohui; Schrag, Deborah; Prigerson, Holly G.

    2015-01-01

    Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic

  6. 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.

  7. Prognostic value of long non-coding RNA MALAT1 in cancer patients.

    PubMed

    Wu, Yihua; Lu, Wei; Xu, Jinming; Shi, Yu; Zhang, Honghe; Xia, Dajing

    2016-01-01

    Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) was identified to be the first long non-coding RNA as a biomarker of independent prognostic value for early stage non-small cell lung cancer patient survival. In recent years, the association between upregulated tissue MALAT1 level and incidence of various cancers including bladder cancer, colorectal cancer, and renal cancer has been widely discussed. The aim of our present study was to assess the potential prognostic value of MALAT1 in various human cancers. PubMed, Embase, Ovid, and Cochrane Library databases were systematically searched, and eligible studies evaluating the prognostic value of MALAT1 in various cancers were included. Finally, 11 studies encompassing 1216 participants reporting with sufficient data were enrolled in the current meta-analysis. The pooled hazard ratio (HR) was 2.05 (95 % confidence interval (CI) 1.64-2.55, p < 0.01) for overall survival (OS) and 2.66 (95 % CI 1.86-3.80, p < 0.01) for disease-free survival (DFS). In conclusion, high tissue MALAT1 level was associated with an inferior clinical outcome in various cancers, suggesting that MALAT1 might serve as a potential prognostic biomarker for various cancers.

  8. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study.

    PubMed Central

    Siewert, J R; Böttcher, K; Stein, H J; Roder, J D

    1998-01-01

    OBJECTIVE: In 1986 a prospective multicenter observation trial in patients with resected gastric cancer was initiated in Germany. An analysis of prognostic factors based on the 10-year survival data is now presented. PATIENTS AND METHODS: A total of 1654 patients treated for gastric cancer between 1986 and 1989 at 19 centers in Germany and Austria were included. The resected specimen were evaluated histopathologically according to a standardized protocol. The extent of lymphadenectomy was classified after surgery based on the number of removed lymph nodes on histopathologic assessment (25 or fewer removed nodes, D1 or standard lymphadenectomy; >25 removed nodes, D2 or extended lymphadenectomy). Endpoint of the study was death. Follow-up is complete for 97% of the included patients (median follow-up of the surviving patients is 8.4 years). Prognostic factors were assessed by multivariate analysis. RESULTS: A complete macroscopic and microscopic tumor resection (R0 resection according to the UICC 1997) could be achieved in 1182 of the 1654 patients (71.5%). The calculated 10-year survival rate in the entire patient population was 26.3% +/- 4.7%; it was 36.1% +/- 1.6% after an R0 resection. In the total patient population there was an independent prognostic effect of the ratio between invaded and removed lymph nodes, the residual tumor (R) category, the pT category, the presence of postsurgical complications, and the presence of distant metastases. Multivariate analysis in the subgroup of patients who had a UICC R0 resection confirmed the nodal status, the pT category, and the presence of postsurgical complications as the major independent prognostic factors. The extent of lymph node dissection had a significant and independent effect on the 10-year survival rate in patients with stage II tumors. This effect was present in the subgroups with (pT2N1) and without (pT3N0) lymph node metastases on standard histopathologic assessment. The beneficial effect of extended

  9. Prognostic implications of normal exercise thallium-201 images

    SciTech Connect

    Wahl, J.; Hakki, A.H.; Iskandrian, A.S.; Kay, H.

    1984-01-01

    The usefulness of exercise-thallium-201 imaging (ETI) in the evaluation of patients (pts) with suspected coronary heart disease (CHD) is well established. A more far-reaching use of the method is, however, in risk stratification. The purpose of this study was to determine the prognosis of pts with normal ETI results. The study group consisted of 432 pts (218 men and 214 women with a mean age of 51 years) who underwent ETI for suspected CHD. Of those, 305 (71%) had typical or atypical angina pectoris and 65% achieved greater than or equal to85% of maximum predicted heart rate. The exercise ECG was positive in 65 pts (15%), inconclusive in 153 (35%) and negative in 214 (50%). At a mean follow-up of 13.5 mos (range 4 to 44), 6 pts had cardiac events: 1 had fatal myocardial infarction (MI) and 5 had non-fatal MI's, (one pt with non-fatal MI had spasm by coronary angiography). Two other pts had coronary artery bypass grafting. Of the 6 pts with events, none had positive exercise ECG's, 2 had typical angina, 2 had atypical angina, and 2 had non-anginal chest pain. The authors conclude the following: (1) normal ETI results identify pts at a very low risk for future cardiac events (death: 0.2%, MI: 1.2%) which is comparable to that reported in pts with chest pain and angiographically normal coronary angiograms, (2) pts with positive exercise ECG's but normal ETI results have good prognosis, none of the 65 pts in this study had cardiac events, and, (3) ETI is a far better prognostic indicator than exercise ECG, because of the high incidence of inconclusive exercise ECG results (35%) and the good prognosis in pts with positive results.

  10. Prognostic value of mitotic index and Bcl2 expression in male breast cancer.

    PubMed

    Lacle, Miangela M; van der Pol, Carmen; Witkamp, Arjen; van der Wall, Elsken; van Diest, Paul J

    2013-01-01

    The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic value. Previous papers on Bcl2 expression in MBC were equivocal, and the prognostic value of Bcl2 combined with mitotic index has not been studied in MBC. The aim of the present study was therefore to investigate the prognostic value of Bcl2 in combination with mitotic index in MBC. Immunohistochemical staining for Bcl2 was performed on tissue microarrays of a total of 151 male breast cancer cases. Mitotic index was scored. The prognostic value of Bcl2 expression and Bcl2/mitotic index combinations was evaluated studying their correlations with clinicopathologic features and their prediction of survival. The vast majority of MBC (94%) showed Bcl2 expression, more frequently than previously described for FBC. Bcl2 expression had no significant associations with clinicopathologic features such as tumor size, mitotic count and grade. In univariate survival analysis, Bcl2 had no prognostic value, and showed no additional prognostic value to tumor size and histological grade in Cox regression. In addition, the Bcl2/mitotic index combination as opposed to FBC did not predict survival in MBC. In conclusion, Bcl2 expression is common in MBC, but is not associated with major clinicopathologic features and, in contrast to FBC, does not seem to have prognostic value, also when combined with mitotic index.

  11. Prognostic value of the Glasgow Prognostic Score in metastatic colorectal cancer in the era of anti-EGFR therapies.

    PubMed

    Dréanic, Johann; Maillet, Marianne; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2013-01-01

    The Glasgow Prognostic Score (GPS), combination of C-reactive protein and albumin, has proven its prognostic value in metastatic colorectal cancer (mCRC) patients receiving conventional cytotoxic therapy. More recently, anti-EGFR therapies have been validated in mCRC and roll forward the patients' overall survival (OS). We aimed to evaluate the prognostic accuracy of the GPS in patients receiving anti-EGFR therapy in addition to conventional chemotherapy. From January 2007 to February 2012, consecutive mCRC patients who received 5-fluorouracil-based chemotherapy plus cetuximab were included in the present analysis. Patients were eligible for the study if they met the following criteria: advanced pathologically proven MCRC, age >18 years, adequate renal function (creatinine clearance >40 ml/min), C-reactive protein and albumin and performance status evaluation before treatment initiation. A total of 49 patients received cetuximab plus 5-fluorouracil-based chemotherapy (colon, n = 34; rectum, n = 15) and were treated with a median follow-up of 35 months (16.5-74.7). Median age was 48 years old. In addition to cetuximab, patients received oxaliplatin- (n = 34, 60%) or irinotecan (n = 15, 30%)-based chemotherapy. At time of diagnosis, 55, 29 and 16% of patients had a GPS of 0 (n = 27), 1 (n = 14) and 2 (n = 8), respectively. Fifty-five, 29 and 14 % of patients add one, two or ≥3 metastatic sites, respectively. Considering two groups (GPS = 0 and GPS ≥1), median progression-free survivals were significantly different (p = 0.0084). Median OS in the GPS 0, 1 and 2 groups were 38.2, 14 and 12.1 months, respectively (p = 0.0093). The results of the present study confirm that the GPS is still a simple and effective prognostic factor in the era of cetuximab therapy in mCRC patients.

  12. Prognostic Significance of Preoperative Circulating Monocyte Count in Patients With Breast Cancer

    PubMed Central

    Wen, Jiahuai; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Abstract Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan–Meier analysis showed that patients with elevated AMC levels (>0.48 × 109/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045–1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II–III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer. PMID:26656374

  13. Prognostic factors of second primary contralateral breast cancer in early-stage breast cancer

    PubMed Central

    LI, ZHENG; SERGENT, FABRICE; BOLLA, MICHEL; ZHOU, YUNFENG; GABELLE-FLANDIN, ISABELLE

    2015-01-01

    The aim of the present study was to investigate the therapeutic outcome of early-stage breast cancer (pT1aN0M0) and to identify prognostic factors for secondary primary contralateral breast cancer (CBC). A total of 85 patients with mammary carcinomas were included. All patients had undergone breast surgery and adjuvant treatment between January 2001 and December 2008 at the Central Hospital of Grenoble University (Grenoble, France). The primary end-points were disease-free survival and secondary CBC, and the potential prognostic factors were investigated. During a median follow-up of 60 months, 10 of the 85 patients presented with secondary primary cancer, of which six suffered with CBC. No patient mortalities were reported. The rates of CBC were 2.35, 3.53 and 7.06% at one, two and five years, respectively. The cumulative univariate analysis showed that microinvasion and family history are potential risk factors for newly CBC. The current study also demonstrated that secondary CBC was more likely to occur in patients with microinvasion or a family history of hte dise. In addition, the systematic treatment of secondary CBC should include hormone therapy. PMID:25435968

  14. The Significance of the Prognostic Nutritional Index in Patients with Completely Resected Non-Small Cell Lung Cancer

    PubMed Central

    Mori, Shunsuke; Usami, Noriyasu; Fukumoto, Koichi; Mizuno, Tetsuya; Kuroda, Hiroaki; Sakakura, Noriaki; Yokoi, Kohei; Sakao, Yukinori

    2015-01-01

    Objectives Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer. Methods We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center. Results The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index. Conclusions The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer. PMID:26356222

  15. Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

    ClinicalTrials.gov

    2016-02-18

    Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  16. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Aust, Stefanie; Knogler, Thomas; Pils, Dietmar; Obermayr, Eva; Reinthaller, Alexander; Zahn, Lisa; Radlgruber, Ilja; Mayerhoefer, Marius Erik; Grimm, Christoph; Polterauer, Stephan

    2015-01-01

    Objective Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients. Methods We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis. Results Muscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively). Conclusion MA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA. PMID:26457674

  17. Gene expression-based prognostic signatures in lung cancer: ready for clinical use?

    PubMed

    Subramanian, Jyothi; Simon, Richard

    2010-04-07

    A substantial number of studies have reported the development of gene expression-based prognostic signatures for lung cancer. The ultimate aim of such studies should be the development of well-validated clinically useful prognostic signatures that improve therapeutic decision making beyond current practice standards. We critically reviewed published studies reporting the development of gene expression-based prognostic signatures for non-small cell lung cancer to assess the progress made toward this objective. Studies published between January 1, 2002, and February 28, 2009, were identified through a PubMed search. Following hand-screening of abstracts of the identified articles, 16 were selected as relevant. Those publications were evaluated in detail for appropriateness of the study design, statistical validation of the prognostic signature on independent datasets, presentation of results in an unbiased manner, and demonstration of medical utility for the new signature beyond that obtained using existing treatment guidelines. Based on this review, we found little evidence that any of the reported gene expression signatures are ready for clinical application. We also found serious problems in the design and analysis of many of the studies. We suggest a set of guidelines to aid the design, analysis, and evaluation of prognostic signature studies. These guidelines emphasize the importance of focused study planning to address specific medically important questions and the use of unbiased analysis methods to evaluate whether the resulting signatures provide evidence of medical utility beyond standard of care-based prognostic factors.

  18. Mean platelet volume provides beneficial diagnostic and prognostic information for patients with resectable gastric cancer

    PubMed Central

    Shen, Xiao-Ming; Xia, You-You; Lian, Lian; Zhou, Chong; Li, Xiang-Li; Han, Shu-Guang; Zheng, Yan; Gong, Fei-Ran; Tao, Min; Mao, Zhong-Qi; Li, Wei

    2016-01-01

    Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related mortalities worldwide. Platelets play an important and multifaceted role in cancer progression. Elevated mean platelet volume (MPV) detected in peripheral blood has been identified in various types of cancer. In the present study, we investigated the application value of MPV in early diagnostic and prognostic prediction in patients with resectable gastric cancer. In total, 168 patients with resectable gastric cancer were included and separated into the gastric cancer and healthy control groups according to median pre-operatic MPV value (MPV low, <10.51 or MPV high, ≥10.51). The results showed that the pre-operatic MPV level was significantly higher in gastric cancer patients compared with the healthy subjects. Low pre-operatic MPV level correlated with improved clinicopathological features, including decreased depth of invasion, less lymphonodus metastasis and early tumor stage. The Kaplan-Meier plots showed that the patients with higher pre-operatic MPV had decreased overall survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted in a significant decrease in the MPV level. The patients whose MPV level decreased following surgery had an improved OS. Multivariate Cox regression analysis revealed that the depth of invasion, lymphonodus metastasis, American Joint Committee on Cancer (AJCC) stage, and changes in MPV following surgery were prognostic factors affecting OS, and the AJCC stage and pre-operatic MPV were prognostic factors affecting DFS. In conclusion, MPV measurement can provide important diagnostic and prognostic results in patients with resectable gastric cancer. PMID:27703523

  19. 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

  20. Methylation of serum SST gene is an independent prognostic marker in colorectal cancer

    PubMed Central

    Liu, Yanqun; Chew, Min Hoe; Tham, Chee Kian; Tang, Choong Leong; Ong, Simon YK; Zhao, Yi

    2016-01-01

    There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MAL were significantly predictive of cancer-specific death (P<0.005 for both). The former was also a significant predictor for tumor recurrence (P=0.007). Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model (P=0.031 and P=0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification. PMID:27725914

  1. Prognostic value of a newly identified MALAT1 alternatively spliced transcript in breast cancer

    PubMed Central

    Meseure, Didier; Vacher, Sophie; Lallemand, François; Alsibai, Kinan Drak; Hatem, Rana; Chemlali, Walid; Nicolas, Andre; De Koning, Leanne; Pasmant, Eric; Callens, Celine; Lidereau, Rosette; Morillon, Antonin; Bieche, Ivan

    2016-01-01

    Background: Epigenetic deregulation is considered as a new hallmark of cancer. The long non-coding RNA MALAT1 has been implicated in several cancers; however, its role in breast cancer is still little known. Methods: We used RT–PCR, in situ hybridisation, and RPPA methods to quantify (i) the full-length (FL) and an alternatively spliced variant (Δsv) of MALAT1, and (ii) a panel of transcripts and proteins involved in MALAT1 pathways, in a large series of breast tumours from patients with known clinical/pathological status and long-term outcome. Results: MALAT1 was overexpressed in 14% (63/446) of the breast tumours. MALAT1-overexpressed tumour epithelial cells showed marked diffuse nuclear signals and numerous huge nuclear speckles. Screening of the dbEST database led to the identification of Δsv-MALAT1, a major alternatively spliced MALAT1 transcript, with a very different expression pattern compared with FL-MALAT1. This alternative Δsv-MALAT1 transcript was mainly underexpressed (18.8%) in our breast tumour series. Multivariate analysis showed that alternative Δsv-MALAT1 transcript is an independent prognostic factor. Δsv-MALAT1 expression was associated with alterations of the pre-mRNAs alternative splicing machinery, and of the Drosha-DGCR8 complex required for non-coding RNA biogenesis. Alternative Δsv-MALAT1 transcript expression was associated to YAP protein status and with an activation of the PI3K-AKT pathway. Conclusions: Our results reveal a complex expression pattern of various MALAT1 transcript variants in breast tumours, and suggest that this pattern of expressions should be taken into account to evaluate MALAT1 as predictive biomarker and therapeutic target. PMID:27172249

  2. 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.

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

    PubMed Central

    Wilczynski, Milosz; 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. PMID:27737015

  4. Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer

    PubMed Central

    Wong, Jocelyn P.; Natrajan, Rachael C.; Yuan, Yinyin; Tan, Aik-Choon; Huang, Paul H.

    2016-01-01

    Tumour cell-extracellular matrix (ECM) interactions are fundamental for discrete steps in breast cancer progression. In particular, cancer cell adhesion to ECM proteins present in the microenvironment is critical for accelerating tumour growth and facilitating metastatic spread. To assess the utility of tumour cell-ECM adhesion as a means for discovering prognostic factors in breast cancer survival, here we perform a systematic phenotypic screen and characterise the adhesion properties of a panel of human HER2 amplified breast cancer cell lines across six ECM proteins commonly deregulated in breast cancer. We determine a gene expression signature that defines a subset of cell lines displaying impaired adhesion to laminin. Cells with impaired laminin adhesion showed an enrichment in genes associated with cell motility and molecular pathways linked to cytokine signalling and inflammation. Evaluation of this gene set in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort of 1,964 patients identifies the F12 and STC2 genes as independent prognostic factors for overall survival in breast cancer. Our study demonstrates the potential of in vitro cell adhesion screens as a novel approach for identifying prognostic factors for disease outcome. PMID:27556857

  5. Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

    PubMed Central

    Walter, Scott D.; Chao, Daniel L.; Feuer, William; Schiffman, Joyce; Char, Devron H.; Harbour, J. William

    2016-01-01

    least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort. CONCLUSIONS AND RELEVANCE Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy. PMID:27123792

  6. ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

    PubMed Central

    Hou, Pingfu; Zhang, Zhe; Zhang, Yafei; Wang, Weimin; Sun, Guixiang; Xu, Lichun; Zhou, Jianwei; Bai, Jin; Zheng, Junnian

    2016-01-01

    ING4, a potential tumor suppressor, is implicated in cell cycle arrest, apoptosis, cell migration and angiogenesis. Here, we investigated the clinical value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this study, we found that ING4 expression was significantly reduced in CRC tissues versus paired normal colon tissues. Moreover, low ING4 expression was significantly associated with increased lymph node metastasis, advanced TNM stage and poor overall survival. Multivariate Cox regression analysis showed that ING4 expression was an independent favourable prognostic factor for CRC (hazard ratio = 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC angiogenesis by suppressing Sp1 expression and transcriptional activity through ubiquitin degradation and down-regulating the expressions of Sp1 downstream pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by inducing p21 expression in despite of p53 status. Our findings imply that reduced ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for the treatment of metastatic CRC. PMID:27806345

  7. Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer

    PubMed Central

    Wang, Jian; Wang, Tongshan; Xu, Jun; Chen, WenJiao; Shi, Wei; Cheng, Jianfeng

    2016-01-01

    Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy. PMID:27478321

  8. Long noncoding RNAs in prostate cancer: overview and clinical implications

    PubMed Central

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  9. Aberrant expression of long noncoding RNA PVT1 and its diagnostic and prognostic significance in patients with gastric cancer.

    PubMed

    Yuan, C L; Li, H; Zhu, L; Liu, Z; Zhou, J; Shu, Y

    2016-01-01

    Emerging evidences indicate that dysregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker, or potential therapeutic targets. LncRNA PVT1 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. This study was to evaluate the expression of PVT1 in GC and further explore its clinical significance.Previous microarray datasets were analyzed to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in human gastric cancer tissues. Expression levels of PVT1 in 111pairs of gastric cancer and adjacent normal tissues, gastric cancer cell lines and gastric cancer juices compared to their corresponding controls were detected by real-time quantitative RT-PCR assay. A receiver operating characteristic (ROC) curve and Kaplan-Meier analysis were constructed to evaluate the diagnostic and prognostic values. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis.PVT1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control, and its up-regulation was significantly correlated to invasion depth (P < 0.001), advanced TNM stage (P = 0.002) and regional lymph nodes metastasis (P < 0.001) in gastric cancer. PVT1 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.728; 95 % confidence interval (CI) = 0.665-0.786, p<0.01]. Kaplan-Meier analysis demonstrated that increased PVT1 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that PVT1 could be an independent prognostic marker. The levels of PVT1 in gastric juice from gastric patients were significantly higher than those from normal subjects (P = 0.03). PVT1 might serve as a

  10. Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.

    PubMed

    Choi, Seyoun; Lee, Keun-Wook; Bang, Soo-Mee; Kim, Sujung; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Park, Young Soo; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Jae-Sung; Oh, Doyeun; Lee, Jong Seok

    2011-12-01

    This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.

  11. 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.

  12. 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

  13. Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma

    PubMed Central

    Kim, Yourha; Kim, Min-Hee; Jeon, Sora; Kim, Jeeyoon; Kim, Chankyung; Bae, Ja Seong

    2017-01-01

    Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients. PMID:28358874

  14. Novel immunological and nutritional-based prognostic index for gastric cancer

    PubMed Central

    Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

    2015-01-01

    AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer. PMID:26019461

  15. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer

    PubMed Central

    Cuzick, J; Yang, Z H; Fisher, G; Tikishvili, E; Stone, S; Lanchbury, J S; Camacho, N; Merson, S; Brewer, D; Cooper, C S; Clark, J; Berney, D M; Møller, H; Scardino, P; Sangale, Z

    2013-01-01

    Background: The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate. Methods: The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer. Results: The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60–4.73; P=3.1 × 10−14). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2–24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses. Conclusion: In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease. PMID:23695019

  16. Prognostic value of serum tumor abnormal protein in gastric cancer patients

    PubMed Central

    LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING

    2016-01-01

    Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802

  17. A population based analysis of prognostic factors in advanced biliary tract cancer

    PubMed Central

    Renouf, Daniel; Lim, Howard

    2014-01-01

    Background Data regarding prognostic factors in advanced biliary tract cancer (BTC) remains scarce. The aim of this study was to review our institutional experience with cisplatin and gemcitabine in advanced BTC as well as to evaluate potential prognostic factors for overall survival (OS). Material and methods Consecutive patients with advanced BTC who initiated palliative chemotherapy with cisplatin and gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using the pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate and multivariate analyses. Results A total of 106 patients were included in the analysis. Median OS was 8.5 months (95% CI: 6.5-10.5). On univariate analysis, poor ECOG performance status (ECOG PS) at diagnosis, primary tumor location (extra-hepatic cholangiocarcinoma, and unknown biliary cancer), and sites of advanced disease (extra-hepatic metastasis) were significantly associated with worse OS (P<0.001, 0.036 and 0.034, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, and prior stent were not significantly associated with OS. On multivariate analysis, ECOG PS 2/3 was the only predictor of poor OS (P<0.001), while primary location (P=0.089) and sites of advanced disease (P=0.079) had a non-significant trend towards prognostic significance. Conclusions In this population based analysis, a poorer performance status was significantly prognostic of worse OS. Although not significant in our analysis, primary tumor location and sites of advanced disease may also have prognostic relevance. PMID:25436121

  18. The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

    PubMed Central

    Xiang, Youqun; Chen, Yizuo; Qu, Jinmiao

    2017-01-01

    Although a few studies have assessed the prognostic value of long noncoding RNA HOTTIP in patients with malignant tumors, the relationship between HOTTIP and clinical outcome of breast cancer remains elusive. The aim of this study is to explore the prognostic significance of HOTTIP in breast cancer patients. A meta-analysis was performed to involve the eligible studies to investigate the association of HOTTIP expression level with outcome in cancer patients. Pooled hazard ratios (HRs) and 95% confidence interval (CI) of HOTTIP for cancer survival were calculated. Five relevant articles involving 460 patients with various solid carcinomas were included in this meta-analysis. For overall survival, high HOTTIP expression could significantly predict worse outcome with the pooled HR of 2.29 (95 % CI 1.72–3.03, P < 0.00001). Furthermore, Gene Expression Omnibus was performed to evaluate the association of HOTTIP expression with the prognosis in breast cancer patients. It was also found an indication that high HOTTIP expression was associated with worse survival in breast cancer patients by microarray analysis (GSE20711, GSE16446 and GSE9195). Finally, association between HOTTIP levels and clinicopathological factors and prognosis was also analyzed in an independent validation cohort including 100 breast cancer cases. HOTTIP expression was correlated with tumor size (P=0.025), lymph node status (P=0.009) and TNM stage (P=0.0001) in the breast cancer validation cohort. The Kaplan-Meier survival curves indicated that breast cancer patients with high HOTTIP expression had worse overall survival (P=0.0139) and disease-free survival (P=0.0003). Multivariate survival analysis based on the Cox proportional hazards model showed that HOTTP is considered as an independent prognostic factor in breast cancer patients. Together, our combined results suggest that high HOTTIP expression may be serving as an unfavorable prognosis predictor for breast cancer patients. PMID:28036281

  19. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer.

    PubMed

    Eggemann, Holm; Ignatov, Tanja; Burger, Elke; Kantelhardt, Eva Johanna; Fettke, Franziska; Thomssen, Christoph; Costa, Serban Dan; Ignatov, Atanas

    2015-10-01

    Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2- expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR- breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052-1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926-1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated.

  20. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    PubMed

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  1. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    PubMed

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  2. Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review

    PubMed Central

    Fan, Gaowei; Zhang, Kuo; Yang, Xin; Ding, Jiansheng; Wang, Zujian; Li, Jinming

    2017-01-01

    The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer. PMID:28187169

  3. Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer

    PubMed Central

    Hwang, Seong Bae; Lee, Hye Yoon; Kim, Hoon Yub

    2012-01-01

    Purpose Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. Methods We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. Results CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). Conclusion CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer. PMID:22493626

  4. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

    PubMed Central

    2012-01-01

    Introduction Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes. Methods Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival. Results Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes. Conclusions CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic

  5. The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer.

    PubMed

    Read, Martin L; Seed, Robert I; Modasia, Bhavika; Kwan, Perkin P K; Sharma, Neil; Smith, Vicki E; Watkins, Rachel J; Bansal, Sukhchain; Gagliano, Teresa; Stratford, Anna L; Ismail, Tariq; Wakelam, Michael J O; Kim, Dae S; Ward, Stephen T; Boelaert, Kristien; Franklyn, Jayne A; Turnell, Andrew S; McCabe, Christopher J

    2016-01-01

    The PTTG1-binding factor (PBF) is a transforming gene capable of eliciting tumor formation in xenograft models. However, the precise role of PBF in tumorigenesis and its prognostic value as a cancer biomarker remain largely uncharacterised, particularly in malignancies outside the thyroid. Here, we provide the first evidence that PBF represents a promising prognostic marker in colorectal cancer. Examination of a total of 39 patients demonstrated higher PBF expression at both the mRNA (P = 0.009) and protein (P < 0.0001) level in colorectal tumors compared to matched normal tissue. Critically, PBF was most abundant in colorectal tumors associated with Extramural Vascular Invasion (EMVI), increased genetic instability (GI) and somatic TP53 mutations, all features linked with recurrence and poorer patient survival. We further demonstrate by glutathione-S-transferase (GST) pull-down and coimmunoprecipitation that PBF binds to the tumor suppressor protein p53, as well as to p53 mutants (Δ126-132, M133K, V197E, G245D, I255F and R273C) identified in the colorectal tumors. Importantly, overexpression of PBF in colorectal HCT116 cells interfered with the transcriptional activity of p53-responsive genes such as mdm2, p21 and sfn. Diminished p53 stability (> 90%; P < 0.01) was also evident with a concurrent increase in ubiquitinated p53. Human colorectal tumors with wild-type TP53 and high PBF expression also had low p53 protein levels (P < 0.05), further emphasizing a putative interaction between these genes in vivo. Overall, these results demonstrate an emerging role for PBF in colorectal tumorigenesis through regulating p53 activity, with implications for PBF as a prognostic indicator for invasive tumors.

  6. Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient

    PubMed Central

    Lin, Xiao-Yan; Zhang, Lian; Zhang, Jia-Xin; Wang, Lian-Xin; Yang, Jun; Ding, Jin-Hua; Pan, Xin; Shao, Zhi-Ming; Biskup, Ewelina

    2016-01-01

    BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis. PMID:27027444

  7. Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient.

    PubMed

    Cai, Feng-Feng; Chen, Su; Wang, Ming-Hong; Lin, Xiao-Yan; Zhang, Lian; Zhang, Jia-Xin; Wang, Lian-Xin; Yang, Jun; Ding, Jin-Hua; Pan, Xin; Shao, Zhi-Ming; Biskup, Ewelina

    2016-05-10

    BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis.

  8. Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

    PubMed Central

    Lee, Yong Joon; Kim, Woo Ram; Han, Jeonghee; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes. PMID:28119863

  9. Prognostic Value of miR-21 in Various Cancers: An Updating Meta-Analysis

    PubMed Central

    Huang, Zebo; Wang, Jian; Zhu, Wei; Shu, Yongqian; Liu, Ping

    2014-01-01

    Background Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. Methods We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Results The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66–2.19) for OS, 1.42 (95% CI: 1.16–1.74) for DFS and 2.2 (95% CI: 1.64–2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18–4.9) for OS. Conclusions Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical. PMID:25019505

  10. Results of chemo-radiotherapy and prognostic factors of small cell lung cancer.

    PubMed

    Shikaura, S; Kawa, S; Yoshida, M; Yonezu, S

    1991-01-01

    We studied the therapeutic results and prognostic factors in 63 cases of small cell lung cancer (SCLC) experienced in our hospital over the past eight years. In the group initially treated with combination chemotherapy using COMP-VAD, the survival period was significantly prolonged. Use of adjuvant radiotherapy from the beginning had no effect on improvement in the survival period, but the period until local recurrences tended to be prolonged. Prognostic factors influencing survival were analyzed by the log rank test and generalized Wilcoxon test and multivariate analysis by the proportional hazard model of Cox. Statistical significance using univariate analysis was found for six factors (PS, clinical stage, LDH, albumin, treatment protocols, treatment response). The strong prognostic factors determined by multivariate analysis were, in the order of importance, chemotherapy protocol, initial PS, and treatment response.

  11. Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery with Nonsmall Cell Lung Cancer.

    PubMed

    Qiu, Chen; Qu, Xiao; Shen, Hongchang; Zheng, Chunlong; Zhu, Linhai; Meng, Long; Du, Jiajun

    2015-01-01

    The prognostic nutritional index (PNI) has been reported to be a prognostic indicator in some malignant tumors. However, its prognostic value in nonsmall cell lung cancer (NSCLC) has not been fully investigated. A retrospective review of 1416 patients with NSCLC who underwent radical surgery between January 2006 and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied. Survival was calculated by the Kaplan-Meier method. The prognostic significance of PNI, together with various clinicopathological factors, was evaluated by multivariate analysis. The optimal cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were significantly more unfavorable than those in patients with PNI 52 or higher (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis suggested that gender (P = 0.026), age (P < 0.001), PNI (P = 0.005), differentiation (P = 0.024), pathology T category (P = 0.003), and pathology N category (P < 0.001) were revealed to be independent prognostic factors. Our results indicate that PNI is an independent predictor of survival for patients undergoing radical surgery with NSCLC.

  12. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers.

    PubMed

    Aradottir, Margret; Reynisdottir, Sigridur T; Stefansson, Olafur A; Jonasson, Jon G; Sverrisdottir, Asgerdur; Tryggvadottir, Laufey; Eyfjord, Jorunn E; Bodvarsdottir, Sigridur K

    2015-01-01

    Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild-type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer-specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23-40.6; p = 0.028). Poor breast cancer-specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19-85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81-51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A

  13. Hyper-Prolactinemia in Men With Idiopathic Dilated Cardiomyopathy: Does It Have any Prognostic Implications?

    PubMed Central

    Naderi, Nasim; Bakhshandeh, Hooman; Ardeshiri, Maryam; Barzegari, Fatemeh; Amin, Ahmad; Taghavi, Sepideh; Maleki, Majid

    2014-01-01

    Background: Prolactin (PRL) has increasingly been recognized to play a stimulatory role in inflammatory response. Recently, studies have reported an increase in prolactin level among patients with chronic heart failure, however, there is conflicting data about its role as a prognostic factor in these patients. Objectives: We aimed to measure PRL level in male patients with idiopathic dilated cardiomyopathy (IDC) and its relationship with some prognostic factors. Patients and Methods: Serum prolactin level was assessed in 33 men with a diagnosis of IDC, left ventricle ejection fraction (LVEF) less than 35% on standard medical therapy for heart failure and New York Heart Association class II-III. Serum NT-Pro BNP (N terminal pro brain natriuretic peptide), hs-CRP (High sensitive C reactive protein) and six-minute walk test (6MWT) were also measured. Our secondary endpoints were mortality, transplantation and hospitalization due to acute heart failure and all patients were followed for one year. Results: The mean age was 33 ± 7 years (24-45 years) and the mean LVEF was 23% ± 6.5. The mean PRL level was 16 ± 7.7 ng/mL (95% confidence interval: 13.3-18.7 ng/mL), which was significantly higher than normal reference values (4.04-15 ng/mL) (P < 0.0001). There was no correlation between PRL levels and pro BNP, hs-CRP or 6MWT test, however, the serum PRL level was slightly higher among patients who died or were hospitalized or transplanted. Conclusions: Considering our study results, prognostic implication of PRL should be questioned. However, it seems that the significant increase in serum PRL in the study population needs more consideration and may have its own pathophysiologic importance. Further studies are recommended for better addressing the role of PRL in chronic heart failure patients. PMID:25478544

  14. Prognostic implications of imaging in atrophic macular degeneration and its use in clinical practice and clinical trial design.

    PubMed

    Lim, Paul Cc; Layton, Christopher J

    2016-07-01

    Clinical prognostic markers in atrophic age-related macular degeneration include the extent of existing atrophy, fundus autofluorescence (FAF) patterns and optical coherence tomography changes in the outer retina/retinal pigment epithelium interface. The prognostic implications of these findings may be used to determine not just the rate of disease progression but also influence the likelihood, magnitude and clinical relevance of therapy responses. FAF phenotypes have been extensively investigated; however, the pathophysiological mechanisms behind their appearance have not been fully elucidated. Optical coherence tomography imaging is additive to FAF imaging in atrophic age-related macular degeneration, allowing the visualization of detail not available through FAF imaging whilst also displaying subtle changes correlating with the FAF phenotypes themselves, thereby giving clues to their histological determinates. The developing understanding of these imaging modalities and consequent development of prognostically useful classification systems have widespread implication in clinical care and clinical trial design.

  15. Identification of Novel Prognostic Genetic Marker in Prostate Cancer

    DTIC Science & Technology

    2001-08-01

    Natl Cancer Inst 1993;85(20):1657-69. 5. Thomas DJ, Robinson M, King P, Hasan T, Charlton R, Martin J, et al. p53 expression and clinical outcome in...microarray to analyse gene expression patterns in human cancer. Nat. Genet. 14, 457-460. 9. Pollack, J. R., Perou, C. M., Alizadeh , A. A., Eisen, M. B

  16. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer

    PubMed Central

    Song, Wei; Wang, Kai; Zhang, Run-jin; Zou, Shu-bing

    2016-01-01

    Abstract Background: Inflammation plays a critical role in the pathogenesis and progression of cancer. A low lymphocyte-to-monocyte ratio (LMR) is reported be a poor prognostic factor in multiple malignancies. We performed a meta-analysis to evaluate the prognostic role of preoperative LMR in colorectal cancer (CRC). Methods: Studies investigating the prognostic role of preoperative LMR on survival in patients with CRC were systematically searched for in MEDLINE, EMBASE, Cochrane databases from inception up to August 2016. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects/random-effects models. Results: A total of nine studies comprising 8626 patients with CRC were included in the meta-analysis. The pooled analysis demonstrated that low LMR was significantly associated with decreased OS (HR: 0.63, 95% CI: 0.56–0.70, P < 0.001) and DFS/RFS (HR: 0.76, 95% CI: 0.68–0.84, P < 0.001). The negative prognostic impact of low LMR on OS was observed in patients with different ethnicity, treatment methods, cut-off values, and across disease stages. Conclusions: This meta-analysis demonstrates that low preoperative LMR is associated with worse survival in patients with CRC. PMID:27930549

  17. Prognostic factors of advanced stage non-small-cell lung cancer.

    PubMed

    Ben Amar, Jihen; Ben Safta, Boutheina; Zaibi, Haifa; Dhahri, Besma; Baccar, Mohamed Ali; Azzabi, Saloua

    2016-05-01

    Background Lung cancer is the main cause of death from cancer in the world. The 5-year survival is about 15%. Despite the progress of medicine the mortality rate decreased only marginally. This poor prognosis is due to late diagnosis. Aim To evaluate overall survival and prognostic factors in patients locally advanced or metastatic non small cell lung cancer (NSCLC). Methods Retrospective study including 180 patients with non-small cell lung cancer hospitalized in the department of Charles Nicolle Hospital of Tunis between January 2007 and December 2014. Results The mean age was 61.5 years with a male predominance (93.3%). The median overall survival was 6 months. The poor prognostic factors were the performans status (PS) and early delays of management (<30 days). The factors that improve survival were surgical treatment and delays of management more than 45 days.  Conclusion The prognostic factors in locally advanced and metastatic NSLC in our patient were: PS, management delay and treatment. These factors should be considered in management of patient with advanced stage NSCLC.

  18. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  19. Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

    PubMed Central

    Franz, Annika; Richter, Rolf; Dragun, Duska; Heidecke, Harald; Dechend, Ralf; Muller, Dominik N.; Sehouli, Jalid; Braicu, Elena I.

    2016-01-01

    Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected. PMID:27660742

  20. Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

    PubMed Central

    Yang, Fang; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhang, Wenwen; Guan, Xiaoxiang

    2016-01-01

    Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44+/CD24-, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44+/CD24- and ALDH1A1 was significantly associated with worse PFS (P = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC. PMID:27994520

  1. Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

    PubMed Central

    Aziz, Sura; Wik, Elisabeth; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

    2017-01-01

    Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996–2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer. PMID:28199370

  2. Recurrent Bleeding in Hemorrhagic Moyamoya Disease : Prognostic Implications of the Perfusion Status

    PubMed Central

    Jo, Kyung-Il; Kim, Min Soo; Yeon, Je Young; Kim, Jong-Soo

    2016-01-01

    Objective Hemorrhagic moyamoya disease (hMMD) is associated with a poor clinical course. Furthermore, poorer clinical outcomes occur in cases of recurrent bleeding. However, the effect of hemodynamic insufficiency on rebleeding risk has not been investigated yet. This study evaluated the prognostic implications of the perfusion status during the clinical course of adult hMMD. Methods This retrospective study enrolled 52 adult hMMD patients between April 1995 and October 2010 from a single institute. Demographic data, clinical and radiologic characteristics, including hemodynamic status using single photon emission computed tomography (SPECT), and follow up data were obtained via a retrospective review of medical charts and imaging. Statistical analyses were performed to explore potential prognostic factors. Results Hemodynamic abnormality was identified in 44 (84.6%) patients. Subsequent revascularization surgery was performed in 22 (42.3%) patients. During a 58-month (median, range 3–160) follow-up assessment period, 17 showed subsequent stroke (hemorrhagic n=12, ischemic n=5, Actuarial stroke rate 5.8±1.4%/year). Recurrent hemorrhage was associated with decreased basal perfusion (HR 19.872; 95% CI=1.196–294.117) and omission of revascularization (10.218; 95%; CI=1.532–68.136). Conclusion Decreased basal perfusion seems to be associated with recurrent bleeding. Revascularization might prevent recurrent stroke in hMMD by rectifying the perfusion abnormality. A larger-sized, controlled study is required to address this issue. PMID:26962416

  3. Long-Term Results and Prognostic Factors of Gastric Cancer Patients with Microscopic Peritoneal Carcinomatosis

    PubMed Central

    Liu, Xiaowen; Cai, Hong; Sheng, Weiqi; Wang, Yanong

    2012-01-01

    Background Clinical significance of microscopic peritoneal carcinomatosis remained unclear. The aim of this study was to evaluate the prognostic value of microscopic peritoneal carcinomatosis in gastric cancer. Methods From 1996 to 2007, 4426 patients underwent gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. The clinical and pathological data were reviewed to identify patients with microscopic peritoneal carcinomatosis (group 1). The clinicopathological features and prognosis were examined. Additionally, 242 stage-matched gastric cancer patients without microscopic peritoneal carcinomatosis (group 2) and 118 with macroscopic peritoneal carcinomatosis (group 3) were selected as control groups. Results Microscopic peritoneal carcinomatosis was found in 121 patients. There were 85 males and 36 females (2.36:1). There was a higher incidence rate of large size tumor (≥5 cm) (P = 0.045), Borrmann IV (P = 0.000), and serosal invasion (P = 0.000) in gastric cancer with microscopic peritoneal carcinomatosis compared with the control group. The 5-year survival rate of gastric cancer with microscopic peritoneal carcinomatosis was 24%, significantly poorer than that of the stage-matched control group but better than that of patients with macroscopic peritoneal carcinomatosis. The independent prognostic factors identified included pathological stage and operative curability. Conclusions The presence of microscopic peritoneal carcinomatosis was associated with worse prognosis for gastric cancer, but curative surgery showed potential to improve prognosis. PMID:22615966

  4. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer.

    PubMed

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer.

  5. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer

    PubMed Central

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer. PMID:27398168

  6. Systematic Analysis of Challenge-Driven Improvements in Molecular Prognostic Models for Breast Cancer

    PubMed Central

    Margolin, Adam A.; Bilal, Erhan; Huang, Erich; Norman, Thea C.; Ottestad, Lars; Mecham, Brigham H.; Sauerwine, Ben; Kellen, Michael R.; Mangravite, Lara M.; Furia, Matthew D.; Vollan, Hans Kristian Moen; Rueda, Oscar M.; Guinney, Justin; Deflaux, Nicole A.; Hoff, Bruce; Schildwachter, Xavier; Russnes, Hege G.; Park, Daehoon; Vang, Veronica O.; Pirtle, Tyler; Youseff, Lamia; Citro, Craig; Curtis, Christina; Kristensen, Vessela N.; Hellerstein, Joseph; Friend, Stephen H.; Stolovitzky, Gustavo; Aparicio, Samuel; Caldas, Carlos; Børresen-Dale, Anne-Lise

    2013-01-01

    Although molecular prognostics in breast cancer are among the most successful examples of translating genomic analysis to clinical applications, optimal approaches to breast cancer clinical risk prediction remain controversial. The Sage Bionetworks–DREAM Breast Cancer Prognosis Challenge (BCC) is a crowdsourced research study for breast cancer prognostic modeling using genome-scale data. The BCC provided a community of data analysts with a common platform for data access and blinded evaluation of model accuracy in predicting breast cancer survival on the basis of gene expression data, copy number data, and clinical covariates. This approach offered the opportunity to assess whether a crowdsourced community Challenge would generate models of breast cancer prognosis commensurate with or exceeding current best-in-class approaches. The BCC comprised multiple rounds of blinded evaluations on held-out portions of data on 1981 patients, resulting in more than 1400 models submitted as open source code. Participants then retrained their models on the full data set of 1981 samples and submitted up to five models for validation in a newly generated data set of 184 breast cancer patients. Analysis of the BCC results suggests that the best-performing modeling strategy outperformed previously reported methods in blinded evaluations; model performance was consistent across several independent evaluations; and aggregating community-developed models achieved performance on par with the best-performing individual models. PMID:23596205

  7. Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.

    PubMed

    Lei, Bo; Zhang, Xian-Yu; Zhou, Jia-Peng; Mu, Guan-Nan; Li, Yi-Wen; Zhang, You-Xue; Pang, Da

    2016-11-01

    In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44(+) mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.

  8. Prognostic value of PDL1 expression in pancreatic cancer.

    PubMed

    Birnbaum, David J; Finetti, Pascal; Lopresti, Alexia; Gilabert, Marine; Poizat, Flora; Turrini, Olivier; Raoul, Jean-Luc; Delpero, Jean-Robert; Moutardier, Vincent; Birnbaum, Daniel; Mamessier, Emilie; Bertucci, François

    2016-11-01

    Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.

  9. Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients

    PubMed Central

    Austrup, F; Uciechowski, P; Eder, C; Böckmann, B; Suchy, B; Driesel, G; Jäckel, S; Kusiak, I; Grill, H-J; Giesing, M

    2000-01-01

    The prognostic value of disseminated tumour cells derived from 353 breast cancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplification and loss of heterozygosity of 13 tumour suppressor genes and 2 proto-oncogenes using DNA from isolated minimal residual cancer cells. Significant correlations were found between genomic alterations of the DCC - and c-erbB-2 genes in disseminated breast cancer cells and actuarial relapse-free survival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosis of recurrent disease. Logistic regression and Cox multivariate analysis led to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncogenes and tumour suppressor genes seems not only to be a useful adjunct in follow up of carcinoma patients but provides also valuable additional individualized prognostic and predictive information in breast cancer patients beyond the TNM system. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11104564

  10. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer

    PubMed Central

    Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin

    2016-01-01

    Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076

  11. Deletion of 8p is an independent prognostic parameter in prostate cancer

    PubMed Central

    Galal, Rami; Möller-Koop, Christina; Barrow, Phillipp; Tsourlakis, Maria Christina; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Steurer, Stefan; Krech, Till; Büscheck, Franziska; Clauditz, Till Sebastian; Beyer, Burkhard; Wilczak, Waldemar; Graefen, Markus; Huland, Hartwig; Minner, Sarah; Schlomm, Thorsten; Sauter, Guido; Simon, Ronald

    2017-01-01

    Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers. PMID:27880722

  12. Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer

    PubMed Central

    Lin, Victor C.; Lu, Te-Ling; Yin, Hsin-Ling; Yang, Sheau-Fang; Lee, Yung-Chin; Liu, Chia-Chu; Huang, Chao-Yuan; Yu, Chia-Cheng; Chang, Ta-Yuan; Huang, Shu-Pin; Bao, Bo-Ying

    2016-01-01

    Folate metabolism has been associated with cancers via alterations in nucleotide synthesis, DNA methylation, and DNA repair. We hypothesized that genetic variants in methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate metabolism, would affect the prognosis of prostate cancer. Three haplotype-tagging single-nucleotide polymorphisms (SNPs) across the MTHFR gene region were genotyped in a cohort of 458 patients with clinically localized prostate cancer treated with radical prostatectomy. One SNP, rs9651118, was associated with disease recurrence, and the association persisted after multivariate analyses adjusting for known risk factors. Public dataset analyses suggested that rs9651118 affects MTHFR expression. Quantitative real-time polymerase chain reaction analysis revealed that MTHFR expression is significantly upregulated in prostate tumor tissues when compared with adjacent normal tissues. Furthermore, overexpression of MTHFR correlates with cancer recurrence and death in two independent publicly available prostate cancer datasets. In conclusion, our data provide rationale to further validate the clinical utility of MTHFR rs9651118 as a biomarker for prognosis in prostate cancer. PMID:27916838

  13. Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer.

    PubMed

    Bin, Wu; He, Wang; Feng, Zhang; Xiangdong, Lu; Yong, Chen; Lele, Kou; Hongbin, Zhang; Honglin, Guo

    2011-02-01

    Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients' survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.

  14. Nestin servers as a promising prognostic biomarker in non-small cell lung cancer

    PubMed Central

    Liu, Fang; Zhang, Yuan; Lu, Ming; Wang, Cong; Li, Qingbao; Gao, Yongsheng; Mu, Dianbin; Cao, Yan; Li, Miaomiao; Meng, Xiangjiao

    2017-01-01

    Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, P<0.001) after controlling the confounding factors. Then we determined the effects of Nestin on cell proliferation, colony formation, invasion, and apoptosis by knockout of Nestin with a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs. PMID:28386364

  15. Nestin servers as a promising prognostic biomarker in non-small cell lung cancer.

    PubMed

    Liu, Fang; Zhang, Yuan; Lu, Ming; Wang, Cong; Li, Qingbao; Gao, Yongsheng; Mu, Dianbin; Cao, Yan; Li, Miaomiao; Meng, Xiangjiao

    2017-01-01

    Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, P<0.001) after controlling the confounding factors. Then we determined the effects of Nestin on cell proliferation, colony formation, invasion, and apoptosis by knockout of Nestin with a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs.

  16. 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

  17. Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery

    PubMed Central

    Roehrig, Andrew T.; Ferrel, Ethan A.; Benincosa, Devon A.; MacKay, Alexander R.; Ling, Benjamin C.; Carlson, Jonathan D.; Demakas, John J.; Wagner, Aaron; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Call, Jason A.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

    2016-01-01

    Background: Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS. Methods: Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS. Results: Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70–80 showed significantly shorter survival than those with KPS 90–100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779). Conclusion: SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients. PMID:27990315

  18. Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer.

    PubMed

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

    Notch signaling pathway includes ligands and Notch receptors, which are frequently deregulated in several human malignancies including ovarian cancer. Aberrant activation of Notch signaling has been linked to ovarian carcinogenesis and progression. In the current study, we used the "Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information from a total of 1306 ovarian cancer patients were used to access the prognostic value of four Notch receptors in ovarian cancer patients. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Notch1 messenger RNA (mRNA) high expression was not found to be correlated to overall survival (OS) for all ovarian cancer, as well as in serous and endometrioid cancer patients followed for 20 years. However, Notch1 mRNA high expression is significantly associated with worsen OS in TP53 wild-type ovarian cancer patients, while it is significantly associated with better OS in TP53 mutation-type ovarian cancer patients. Notch2 mRNA high expression was found to be significantly correlated to worsen OS for all ovarian cancer patients, as well as in grade II ovarian cancer patients. Notch3 mRNA high expression was found to be significantly correlated to better OS for all ovarian cancer patients, but not in serous cancer patients and endometrioid cancer patients. Notch4 mRNA high expression was not found to be significantly correlated to OS for all ovarian cancer patients, serous cancer patients, and endometrioid cancer patients. These results indicate that there are distinct prognostic values of four Notch receptors in ovarian cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of ovarian cancer and for developing tools to more accurately predict their prognosis. Based on our results, Notch1 could be a potential drug target of TP53 wild-type ovarian cancer and Notch2 could be a potential drug

  19. Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

    PubMed

    Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

    2015-07-01

    Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

  20. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence

    PubMed Central

    Oczko-Wojciechowska, Małgorzata; Barczyński, Marcin

    2016-01-01

    Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30–80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and

  1. Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer.

    PubMed

    Green, Andrew R; Soria, D; Powe, D G; Nolan, C C; Aleskandarany, M; Szász, M A; Tőkés, A M; Ball, G R; Garibaldi, J M; Rakha, E A; Kulka, J; Ellis, I O

    2016-05-01

    The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditional NPI. This study aimed to determine prognostic capability of the NPI+ in predicting risk of development of distant disease. A well-characterised series of 1073 primary early-stage BC cases treated in Nottingham and 251 cases from Budapest were immunohistochemically assessed for cytokeratin (Ck)5/6, Ck18, EGFR, oestrogen receptor (ER), progesterone receptor, HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class and prognostic scores were assigned using individual algorithms for each biological class incorporating clinicopathologic parameters and investigated in terms of prediction of distant metastases-free survival (MFS). The NPI+ identified distinct prognostic groups (PG) within each molecular class which were predictive of MFS providing improved patient outcome stratification superior to the traditional NPI. NPI+ PGs, between series, were comparable in predicting patient outcome between series in luminal A, basal p53 altered and HER2+/ER+ (p > 0.01) tumours. The low-risk groups were similarly validated in luminal B, luminal N, basal p53 normal tumours (p > 0.01). Due to small patient numbers the remaining PGs could not be validated. NPI+ was additionally able to predict a higher risk of metastases at certain distant sites. This study may indicate the NPI+ as a useful tool in predicting the risk of metastases. The NPI+ provides accurate risk stratification allowing improved individualised clinical decision making for breast cancer.

  2. The Expression and Prognostic Significance of Retinoic Acid Metabolising Enzymes in Colorectal Cancer

    PubMed Central

    Brown, Gordon T.; Cash, Beatriz Gimenez; Blihoghe, Daniela; Johansson, Petronella; Alnabulsi, Ayham; Murray, Graeme I.

    2014-01-01

    Colorectal cancer is one of the most common types of cancer with over fifty percent of patients presenting at an advanced stage. Retinoic acid is a metabolite of vitamin A and is essential for normal cell growth and aberrant retinoic acid metabolism is implicated in tumourigenesis. This study has profiled the expression of retinoic acid metabolising enzymes using a well characterised colorectal cancer tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosal samples. Immunohistochemistry was performed on the tissue microarray using monoclonal antibodies which we have developed to the retinoic acid metabolising enzymes CYP26A1, CYP26B1, CYP26C1 and lecithin retinol acyl transferase (LRAT) using a semi-quantitative scoring scheme to assess expression. Moderate or strong expression of CYP26A1was observed in 32.5% of cancers compared to 10% of normal colonic epithelium samples (p<0.001). CYP26B1 was moderately or strongly expressed in 25.2% of tumours and was significantly less expressed in normal colonic epithelium (p<0.001). CYP26C1 was not expressed in any sample. LRAT also showed significantly increased expression in primary colorectal cancers compared with normal colonic epithelium (p<0.001). Strong CYP26B1 expression was significantly associated with poor prognosis (HR = 1.239, 95%CI = 1.104–1.390, χ2 = 15.063, p = 0.002). Strong LRAT was also associated with poorer outcome (HR = 1.321, 95%CI = 1.034–1.688, χ2 = 5.039, p = 0.025). In mismatch repair proficient tumours strong CYP26B1 (HR = 1.330, 95%CI = 1.173–1.509, χ2 = 21.493, p<0.001) and strong LRAT (HR = 1.464, 95%CI = 1.110–1.930, χ2 = 7.425, p = 0.006) were also associated with poorer prognosis. This study has shown that the retinoic acid metabolising enzymes CYP26A1, CYP26B1 and LRAT are significantly overexpressed in colorectal cancer and that CYP26B1 and LRAT are

  3. Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis

    PubMed Central

    Chi, Jun-Lin; Li, Yuan; Yang, Lie; Yu, Yong-Yang; Sun, Xiao-Feng; Zhou, Zong-Guang

    2016-01-01

    The lymph node ratio (LNR) (i.e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71–2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14–3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems. PMID:27662659

  4. 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.

  5. The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

    SciTech Connect

    Maduro, John H. Noordhuis, Maartje G.; Hoor, Klaske A. ten; Pras, Elisabeth; Arts, Henriette J.G.; Eijsink, Jasper J.H.; Hollema, Harry; Mom, Constantijne H.; Jong, Steven de; Vries, Elisabeth G.E. de; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2009-09-01

    Purpose: Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervical cancer and to determine their predictive and prognostic value. Methods and Materials: Tissue microarrays were constructed from tumors of 645 cervical cancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival. Results: Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p {<=}0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival. Conclusions: Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervical cancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.

  6. 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

  7. Prognostic and predictive response factors in colorectal cancer patients: between hope and reality.

    PubMed

    De Divitiis, Chiara; Nasti, Guglielmo; Montano, Massimo; Fisichella, Rossella; Iaffaioli, Rosario Vincenzo; Berretta, Massimiliano

    2014-11-07

    Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature.

  8. Proliferating cell nuclear antigen (PCNA) immunostaining--a prognostic factor in ovarian cancer?

    PubMed Central

    Thomas, H.; Nasim, M. M.; Sarraf, C. E.; Alison, M. R.; Love, S.; Lambert, H. E.; Price, P.

    1995-01-01

    The measurement of tumour cell proliferation is becoming increasingly recognised in defining prognostic groups. Proliferating cell nuclear antigen (PCNA) immunolocalisation can be used as an index of cell proliferation and may define the extent of departure from normal growth control. The monoclonal antibody PC10 stains PCNA in archival paraffin-embedded tissue. This study investigates its potential as a prognostic marker in early and advanced ovarian cancer. A three-stage immunoperoxidase technique was developed to detect the monoclonal antibody PC10. Archival paraffin-embedded tissue from 19 stage I ovarian tumours (13 malignant and six borderline) and 79 advanced (stage IIb-IV) ovarian tumours (patients entered into the Third North-West Thames Ovarian Cancer Trial) was immunostained with PC10. PC10 immunostaining was performed successfully in 91.8% of cases. The PC10 labelling index (PC10 LI) ranged from 1.5% to 88% with a mean value of 47.4%. Stage I borderline tumours had significantly lower PCNA labelling indexes than stage I malignant tumours (P < 0.048). In advanced disease there was an inverse correlation between PC10 and overall survival, and in those patients who underwent good debulking surgery (37 patients with disease < 2 cm diameter) a low PC10 value (< 36.5%) correlated with improved survival (log-rank trend test for survival, chi 2 = 5.75, P = 0.017). PCNA immunostaining defines a good prognostic subgroup in adequately debulked patients with ovarian cancer. Images Figure 1 PMID:7841053

  9. MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer.

    PubMed

    Sondermann, Adriana; Andreghetto, Flavia Maziero; Moulatlet, Ana Carolina Bernardini; da Silva Victor, Elivane; de Castro, Marilia Germanos; Nunes, Fábio Daumas; Brandão, Lenine Garcia; Severino, Patricia

    2015-08-01

    Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.

  10. Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors

    PubMed Central

    Uusitalo, Elina; Kallionpää, Roope A; Kurki, Samu; Rantanen, Matti; Pitkäniemi, Janne; Kronqvist, Pauliina; Härkönen, Pirkko; Huovinen, Riikka; Carpen, Olli; Pöyhönen, Minna; Peltonen, Sirkku; Peltonen, Juha

    2017-01-01

    Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P=0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1. PMID:27931045

  11. Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential.

    PubMed

    Stelma, Tamara; Chi, Alicia; van der Watt, Pauline J; Verrico, Annalisa; Lavia, Patrizia; Leaner, Virna D

    2016-04-01

    The Karyopherin superfamily is a major class of soluble transport receptors consisting of both import and export proteins. The trafficking of proteins involved in transcription, cell signalling and cell cycle regulation among other functions across the nuclear membrane is essential for normal cellular functioning. However, in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors are some ways in which the Karyopherin proteins are dysregulated. The value of nuclear transporters in the diagnosis, prognosis and treatment of cancer is currently being elucidated with recent studies highlighting their potential as biomarkers and therapeutic targets.

  12. MDSCs in cancer: Conceiving new prognostic and therapeutic targets.

    PubMed

    De Sanctis, Francesco; Solito, Samantha; Ugel, Stefano; Molon, Barbara; Bronte, Vincenzo; Marigo, Ilaria

    2016-01-01

    The incomplete clinical efficacy of anti-tumor immunotherapy can depend on the presence of an immunosuppressive environment in the host that supports tumor progression. Tumor-derived cytokines and growth factors induce an altered hematopoiesis that modifies the myeloid cell differentiation process, promoting proliferation and expansion of cells with immunosuppressive skills, namely myeloid derived suppressor cells (MDSCs). MDSCs promote tumor growth not only by shaping immune responses towards tumor tolerance, but also by supporting several processes necessary for the neoplastic progression such as tumor angiogenesis, cancer stemness, and metastasis dissemination. Thus, MDSC targeting represents a promising tool to eliminate host immune dysfunctions and increase the efficacy of immune-based cancer therapies.

  13. The prognostic impact of age in different molecular subtypes of breast cancer.

    PubMed

    Liedtke, Cornelia; Rody, Achim; Gluz, Oleg; Baumann, Kristin; Beyer, Daniel; Kohls, Eva-Beatrice; Lausen, Kerstin; Hanker, Lars; Holtrich, Uwe; Becker, Sven; Karn, Thomas

    2015-08-01

    Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.

  14. Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer.

    PubMed

    Xu, Lihua; Peng, Sida; Huang, Qunai; Liu, Yu; Jiang, Hua; Li, Xi; Wang, Jiani

    2016-10-01

    Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC). However, data regarding its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study was to investigate CAP2 expression and its prognostic significance in breast cancer. CAP2 expression at the mRNA and protein levels was examined by real‑time quantitative-polymerase chain reaction and western blotting in 10 paired breast cancer tissues and adjacent normal tissues. The expression level of CAP2 protein in normal breast epithelial cells and breast cancer cell lines was quantified by western blotting. CAP2 protein expression was analyzed in paraffin‑embedded breast cancer samples, paired adjacent non‑tumor and normal breast tissues by immunohistochemical analysis. Statistical analyses were also performed to evaluate the clinicopathological significance of CAP2 expression. The results showed that the expression of CAP2 mRNA and protein was higher in breast cancer than that noted in the adjacent normal tissues in 10 paired samples. The expression level of CAP2 protein in breast cancer cell lines was higher than that in normal breast epithelial cells. In paraffin‑embedded tissue samples, the expression of CAP2 was higher in breast cancer than that found in the adjacent non‑cancerous tissues and normal breast tissues. Compared with the adjacent non‑cancerous tissues, overexpression of CAP2 was detected in 29.4% (37/126) of the patients. Overexpression of CAP2 was significantly associated with progesterone receptor (PR) expression (p<0.05), and decreased overall survival (OS) (p<0.05). In multivariate analysis, expression of CAP2 was an independent prognostic factor for OS [hazard ratio (HR), 4.821; 95% confidence interval (CI), 2.442‑9.518; p<0.001]. CAP2 is upregulated in breast cancer and is associated with the expression of PR and patient survival. CAP2 may serve as a prognostic indicator for patients

  15. The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers

    PubMed Central

    2016-01-01

    The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer. PMID:27688722

  16. Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer

    PubMed Central

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Iseki, Yasuhito; Ikeya, Tetsuro; Hirakawa, Kosei

    2017-01-01

    A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

  17. A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

    PubMed Central

    Hang, Bo; Zou, Xiaoping; Mao, Jian-Hua

    2016-01-01

    Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system. PMID:27419373

  18. Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer

    PubMed Central

    Gomez, Christian R.; Kosari, Farhad; Munz, Jan-Marie; Schreiber, Claire A.; Knutson, Gaylord J.; Ida, Cristiane M.; El Khattouti, Abdelouahid; Karnes, R. Jeffrey; Cheville, John C.; Vasmatzis, George; Vuk-Pavlović, Stanimir

    2013-01-01

    Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia–regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p≤0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP. PMID:24349376

  19. The recurrence frequency of breast cancer and its prognostic factors in Iranian patients

    PubMed Central

    Shahriari-Ahmadi, Ali; Arabi, Mohsen; Payandeh, Mehrdad; Sadeghi, Masoud

    2017-01-01

    Background: Recurrent breast cancer (BC) after initial treatments is usually associated with poor outcome. The objective of this study is to evaluate baseline characteristics of BC patients to determine their prognostic influence of recurrences. Materials and Methods: In this retrospective study of 481 BC patients, 182 patients who had recurrence within the first, second, or third 5 years after diagnosis were included in the study. The significant prognostic factors associated with late or very late recurrence were selected according to the Akaike Information Criterion. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. Also, very late recurrence was defined as initial recurrence after 10 years. Results: During the follow-up period, 182 recurrences occurred (local recurrence or distant metastasis). All patients were treated with chemotherapy and radiotherapy and the patients with estrogen receptor (ER)- or progesterone receptor (PR)-positive had hormone therapy. There was a significant correlation between histological grade and receptors status with recurrence. In binary logistic regression analysis, ER and PR were significant prognostic factors for early recurrence. Conclusion: High histological grade and immunohistochemical markers (ER- and PR-negative or human epidermal growth factor receptor 2-positive) are risk factors for recurrence, especially in early recurrence and also between of them, ER is the more significant prognostic factor in early recurrence.

  20. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  1. HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

    PubMed Central

    Li, Huijun; Chen, Qi; Song, Ruixiang; Zhao, Lin

    2016-01-01

    As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer. PMID:27391431

  2. The Eag potassium channel as a new prognostic marker in ovarian cancer

    PubMed Central

    2010-01-01

    Background Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression. Objectives To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation. Methods The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3). Results We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K+ channel blockers. Conclusion This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer. PMID:21138547

  3. 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.

  4. Prognostic and predictive significance of MSI in stages II/III colon cancer.

    PubMed

    Saridaki, Zacharenia; Souglakos, John; Georgoulias, Vassilis

    2014-06-14

    In colon cancer, classic disease staging remains the key prognosis and treatment determinant. Although adjuvant chemotherapy has an established role in stage III colon cancer patients, in stage II it is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features. Patients with stage II tumors form a highly heterogeneous group, with five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4% (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging, and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed. The stronger candidate in this category seems to be microsatellite instability (MSI). The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stage II colorectal cancer patients in order to contribute in treatment decision-making regarding chemotherapy administration. The hypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address. Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature, and the matter is far from being settled. In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stage II and stage III colon cancer patients.

  5. Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

    PubMed Central

    Qian, Yun; Sang, Yiwen; Wang, Frederick X.C.; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

    2016-01-01

    Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer. PMID:27750217

  6. Identification of Novel Prognostic Genetic Markers in Prostate Cancer

    DTIC Science & Technology

    2000-02-01

    early access to new sequence data from the Celera Genomics (http://www.celera.com). We will select UniGene EST contig clusters and predicted genes which...and Macoska, J.A. (1998) Homozygous and Frequent Deletion of Proximal 8p Sequences in Human Prostate Cancers: Identification of a Potential Tumor...correlates with genome instability in human papillomavirus 16 E7 transformed human uroepithelial cells. Oncogene. 14:551-560. 20.) Sutherland, G.R

  7. The prognostic role of quality of life assessment in breast cancer.

    PubMed

    Staren, Edgar D; Gupta, Digant; Braun, Donald P

    2011-01-01

    While the use of quality of life (QoL) assessments has been increasing in oncology, few studies have examined the prognostic significance of QoL in breast cancer. We investigated the association between QoL at presentation and survival in breast cancer. We examined 1,511 breast cancer patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using the validated survey instrument EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of QoL after controlling for the effects of age, tumor stage, and prior treatment history. Mean age at presentation was 52.5 years. There were 590 analytic and 921 non-analytic patients. Patient stage of disease at diagnosis was I, 335; II, 591; III, 290; IV, 159; and 136 indeterminate. Median overall survival was 32.8 months (95% CI: 27.6-38.0). On univariate analysis, QoL function and symptom scales that were predictive of survival were physical (p < 0.001), role (p < 0.001), cognitive (p = 0.003), social (p < 0.001), fatigue (p < 0.001), nausea/vomiting (p < 0.001), pain (p < 0.001), dyspnea (p < 0.001), loss of appetite (p < 0.001), and constipation (p < 0.001). On multivariate analyses, only role function (degree of impairment of work and/or leisure/hobby related activities) was significantly associated with survival. This study suggests that baseline QoL (in particular, the role function) provides useful prognostic information in breast cancer.

  8. Prognostic impact of vitamin B6 metabolism in lung cancer.

    PubMed

    Galluzzi, Lorenzo; Vitale, Ilio; Senovilla, Laura; Olaussen, Ken André; Pinna, Guillaume; Eisenberg, Tobias; Goubar, Aïcha; Martins, Isabelle; Michels, Judith; Kratassiouk, Gueorgui; Carmona-Gutierrez, Didac; Scoazec, Marie; Vacchelli, Erika; Schlemmer, Frederic; Kepp, Oliver; Shen, Shensi; Tailler, Maximilien; Niso-Santano, Mireia; Morselli, Eugenia; Criollo, Alfredo; Adjemian, Sandy; Jemaà, Mohamed; Chaba, Kariman; Pailleret, Claire; Michaud, Mickaël; Pietrocola, Federico; Tajeddine, Nicolas; de La Motte Rouge, Thibault; Araujo, Natalia; Morozova, Nadya; Robert, Thomas; Ripoche, Hugues; Commo, Frederic; Besse, Benjamin; Validire, Pierre; Fouret, Pierre; Robin, Angélique; Dorvault, Nicolas; Girard, Philippe; Gouy, Sébastien; Pautier, Patricia; Jägemann, Nora; Nickel, Ann-Christin; Marsili, Sabrina; Paccard, Caroline; Servant, Nicolas; Hupé, Philippe; Behrens, Carmen; Behnam-Motlagh, Parviz; Kohno, Kimitoshi; Cremer, Isabelle; Damotte, Diane; Alifano, Marco; Midttun, Oivind; Ueland, Per Magne; Lazar, Vladimir; Dessen, Philippe; Zischka, Hans; Chatelut, Etienne; Castedo, Maria; Madeo, Frank; Barillot, Emmanuel; Thomale, Juergen; Wistuba, Ignacio Ivan; Sautès-Fridman, Catherine; Zitvogel, Laurence; Soria, Jean-Charles; Harel-Bellan, Annick; Kroemer, Guido

    2012-08-30

    Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

  9. [New prognostic and predictive markers for breast cancer].

    PubMed

    Wachter, D L

    2016-11-01

    Breast cancer can be divided into four molecular subtypes with different prognoses using immunohistochemical markers in the routine clinicopathological work-up. The protein Ki-67 is of central importance in this context, in particular to distinguish between luminal A and luminal B carcinomas. Determination of the Ki-67 index of a carcinoma also allows a prediction of the likelihood of the response to chemotherapy. Additionally, the expression of certain cytokeratins in tumor cells is associated with a poor response to chemotherapy. The heterogeneity of molecular subtypes with regard to the histological appearance indicates an even greater diversity of breast cancer. We were able to show that a high proportion of luminal B carcinomas display neuroendocrine differentiation. Further studies with particular emphasis on histomorphological criteria should be performed to attain a more accurate classification of breast cancer and to pave the way towards targeted therapies for a better prognosis in the future.

  10. Prognostic value of regulator of G-protein signaling 6 in colorectal cancer.

    PubMed

    Luo, Yang; Qin, Shao-Lan; Yu, Min-Hao; Mu, Yi-Fei; Wang, Zheng-Shi; Zhong, Ming

    2015-12-01

    Reprogrammed metabolism is a hallmark of cancer cells. Regulator of G-protein signaling 6 (RGS6), which is frequently down-regulated in multiple human malignancies, has been demonstrated to play a critical function in energy metabolism, cell apoptosis and tumorigenesis. However, limited knowledge is known about the expression pattern and prognostic value of RGS6 in colorectal cancer (CRC). In this study, we first observed that RGS6 mRNA and protein is commonly downregulated in 32 paired CRC tissues compared with their normal counterparts. Furthermore, by a large scale of immunohistochemical analysis in a tissue microarray containing 310 cases of CRC specimens, we demonstrated that the protein expression of RGS6 expression is downregulated in 40.97% (127/310) samples and detected that decreasing RGS6 expression is closely correlated with enhanced tumor size, CEA level, T classification, TNM stage, and easier lymphatic and distant metastasis. Meanwhile, Kaplan-Meier survival analysis showed that CRC patients with a lower RGS6 expression have a poorer clinical outcome than those with a higher RGS6 expression. Multivariate Cox regression analysis revealed that RGS6, lymphatic metastasis and distant metastasis are the independent prognostic factors for overall survival rate of CRC patients. Taken together, our studies reveal the prognostic value of RGS6 in CRC and support that RGS6 may act as a molecular target for CRC treatment.

  11. Prognostic value of amphiregulin and epiregulin mRNA expression in metastatic colorectal cancer patients

    PubMed Central

    You, Zhai; Qiong, Qian; Jun, Zhou

    2016-01-01

    Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC). In addition, RAS status was assessed. Relevant articles were identified by searching the EMBASE, PubMed, and Cochrane Library databases. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Nine studies involving 2167 patients were included in this meta-analysis. High AREG expression was associated with longer overall survival (OS) and progression-free survival (PFS). High EREG expression was also associated with prolonged OS and PFS. In RAS wild-type (WT) patients who received anti-EGFR therapy, high AREG and EREG expression was associated with longer OS. Our results indicate that high AREG and EREG mRNA expression are independent favorable prognostic biomarkers in mCRC. The expression of these ligands should be considered when evaluating prognoses in RAS-WT patients receiving anti-EGFR therapy. PMID:27344184

  12. [DNA flow cytometry is a useful prognostic guide in the treatment of breast cancer.].

    PubMed

    Gudlaugsdottir, S; Sigurdsson, H; Agnarsson, B A; Jonasson, J G; Kristjansdottir, S; Baldursson, G; Bjornsson, S; Sveinsson, T; Egilsson, V

    1996-02-01

    It is widely agreed that the presence or absence of axillary lymph-node involvement (N) is the most reliable predictor of relapse or survival in breast cancer, together with tumor size (T) and the presence or absence of distant metastasis (M). These prognostic factors are the cornerstones of the TNM staging system. The aim of the present study was to ascertain, in all patients diagnosed with invasive primary breast cancer in Iceland during the years 1981-84 (n=347), whether flow cytometric DNA analysis of ploidy status and fraction of cells in the S-phase contribute prognostic information, addi nottional to that obtained with TNM staging variables. Paraffin fixed tumor material was available from 340 patients (98%) and DNA ploidy and S-phase fraction was assessed with flow cytometry. DNA ploidy could be analysed in 98% of tumor samples (n=334), of which 114 (34%) were diploid and 220 (66%) non-diploid. S-phase fraction could be analysed in 97% of the tumor samples (n=329), the median S-phase value was 7.0%, and was higher in non-diploid than diploid tumors (p<0.0001, 9.3% vs. 2.7%). Median duration of patient follow-up was 7.5 years. The disease-free survival at that point of time was 15% higher in patients with diploid tumors than non-diploid ones (p=0.004, 69% vs 54%). Similar survival comparison in relation to S-phase fraction was 30% when the median S-phase value was used as cut-off point (p<0.0001, S-phase<7.0% being 74% vs. S-phase ;7.0% being 44%). Multivariate analyses with regard to breast cancer survival and disease-free survival, which included both ploidy status and S-phase categories adjusting for age, tumor size and lymph node involvement, showed the S-phase value categories to be independent prognostic variables (p<0.0001). Patients with high S-phase tumors had a three-fold higher risk of recurrence than patients with low S-phase tumors. Ploidy status was not an independent prognostic variable, if however the S-phase categories were excluded from

  13. Expression of CRM1 and CDK5 shows high prognostic accuracy for gastric cancer

    PubMed Central

    Sun, Yu-Qin; Xie, Jian-Wei; Xie, Hong-Teng; Chen, Peng-Chen; Zhang, Xiu-Li; Zheng, Chao-Hui; Li, Ping; Wang, Jia-Bin; Lin, Jian-Xian; Cao, Long-Long; Huang, Chang-Ming; Lin, Yao

    2017-01-01

    AIM To evaluate the predictive value of the expression of chromosomal maintenance (CRM)1 and cyclin-dependent kinase (CDK)5 in gastric cancer (GC) patients after gastrectomy. METHODS A total of 240 GC patients who received standard gastrectomy were enrolled in the study. The expression level of CRM1 and CDK5 was detected by immunohistochemistry. The correlations between CRM1 and CDK5 expression and clinicopathological factors were explored. Univariate and multivariate survival analyses were used to identify prognostic factors for GC. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters. RESULTS The expression of CRM1 was significantly related to size of primary tumor (P = 0.005), Borrmann type (P = 0.006), degree of differentiation (P = 0.004), depth of invasion (P = 0.008), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and distant metastasis (P = 0.015). The expression of CDK5 was significantly related to sex (P = 0.048) and Lauren’s classification (P = 0.011). Multivariate Cox regression analysis identified that CRM1 and CDK5 co-expression status was an independent prognostic factor for overall survival (OS) of patients with GC. Integration of CRM1 and CDK5 expression could provide additional prognostic value for OS compared with CRM1 or CDK5 expression alone (P = 0.001). CONCLUSION CRM1 and CDK5 co-expression was an independent prognostic factors for GC. Combined CRM1 and CDK5 expression could provide a prognostic model for OS of GC. PMID:28373767

  14. Synchronous, bilateral breast cancer: prognostic value and incidence.

    PubMed

    Jobsen, J J; van der Palen, J; Ong, F; Meerwaldt, J H

    2003-04-01

    The purpose of this study was to address the question whether patients with bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and survival than patients with primarily unilateral breast cancer (UBC) following breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were registered in the Radiotherapy Department of the Medisch Spectrum Twente. We defined synchronous a BBC as cancer diagnosed in both breasts at the same time or within a period of 3 months of diagnosis of the first tumor. One thousand seven hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of patients with BBC showed more tubular carcinoma (P=0.029) and medially located tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3% and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were 26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively, after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively). Patients with BBC have a higher rate of distant metastasis and a worse DSS than those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach any more definitive conclusions on outcome and treatment.

  15. Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer

    PubMed Central

    Banys-Paluchowski, M.; Schneck, H.; Blassl, C.; Schultz, S.; Meier-Stiegen, F.; Niederacher, D.; Krawczyk, N.; Ruckhaeberle, E.; Fehm, T.; Neubauer, H.

    2015-01-01

    Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumorsʼ characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer. PMID:25914415

  16. Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

    PubMed Central

    Xu, Feng; Li, Mengxin; Zhang, Chao; Cui, Jianxiu; Liu, Jun; Li, Jie; Jiang, Hongchuan

    2017-01-01

    The prognostic significance of COX-2 in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. PubMed, EMBASE, Web of Science, the Ovid Database and Grey literature were systematically searched up to May 2016. Twenty-one studies including 6739 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of COX-2 expression was significant when comparing the lymph node positive group to negative group (OR = 1.76, 95% CI [1.30, 2.39]) and the tumor size ≥ 2cm group to the tumor size < 2cm group (OR = 1.71, 95% CI [1.22, 2.39]). None of other clinicopathological parameters such as the ER status, PR status, HER2 status and the vascular invasion status were associated with COX-2 overexpression. The detection of COX-2 was significantly correlated with the disease-free survival (DFS) of patients (HR = 1.58, 95% CI [1.23, 2.03]) and the overall survival (OS) of patients (HR = 1.51, 95% CI [1.31, 1.72]). Our meta-analysis demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis. PMID:27999206

  17. Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

    PubMed Central

    Liu, Yongping; Ling, Yang; Qi, Qiufeng; Lan, Feng; Zhu, Ming; Zhang, Yaping; Bao, Yanqing; Zhang, Changsong

    2017-01-01

    The identification of circulating tumor cells (CTCs) may provide important prognostic information in several types of solid tumors, including gastric cancer. The aim of this study was to investigate whether CTC count may be used to predict survival in patients with advanced gastric cancer treated with chemotherapy. The CELLection™ Epithelial Enrich kit was used to isolate and purify CTCs from samples of peripheral blood. Immunofluorescent staining was used for CTC counting. High CTC counts were associated with poor tumor differentiation and high serum CEA levels (P=0.021 and 0.005, respectively). After 3 months, 16 patients with decreasing CTC counts after the first cycle of chemotherapy obtained complete response, partial response or stable disease, while 13 patients with increasing CTC counts developed progressive disease. The patients with decreasing CTC counts also exhibited longer progression-free survival (PFS) (P≤0.001) and overall survival (OS) (P=0.002) compared with those with increasing CTC counts. Among all 59 patients, those with a CTC count of ≤2 cells/5 ml blood exhibited longer PFS (P≤0.001) and OS (P≤0.001) compared with those with a CTC count of >2 cells/5 ml blood. The multivariate analysis suggested that an increase of the CTC count after the first cycle of chemotherapy was only an independent prognostic marker of poor PFS (P=0.019). However, a baseline CTC count of >2 cells/5 ml blood was an independent poor prognostic marker for PFS (P=0.008) and OS (P=0.001) in all 59 patients. Our study suggested that patients with a low baseline CTC count or decrease of the CTC count after the first cycle of chemotherapy may benefit significantly from palliative chemotherapy. In conclusion, CTC count may be a good chemotherapy monitoring marker and an ideal prognostic marker for patients receiving palliative chemotherapy. PMID:28357102

  18. Micrometastatic disease in breast cancer: clinical implications.

    PubMed

    Ignatiadis, Michail; Georgoulias, Vassilis; Mavroudis, Dimitris

    2008-12-01

    The presence of bone marrow disseminated tumour cells (DTCs) was shown to predict poor clinical outcome in early breast cancer. However, peripheral blood is easier to obtain and allows for serial monitoring of minimal residual disease. Towards this aim, circulating tumour cells (CTCs) in the blood are detected using either direct methods, mainly antibody-based assays (immunocytochemistry, immunofluorescence and flow cytometry), or indirect methods, mainly nucleic acid-based assays (detection of mRNA transcripts by reverse transcriptase polymerase chain reaction, RT-PCR). The detection of CTCs using RT-PCR for CK19 was shown to be an independent prognostic factor in women with early breast cancer. Furthermore, considerable progress has been accomplished in genotyping, phenotyping and profiling micrometastatic cells. The challenge now is to integrate minimal residual disease as a prognostic and predictive tool in the management of breast cancer. This requires the standardisation of micrometastatic cell detection and characterisation, which will allow the incorporation of CTCs/DTCs into prospective clinical trials testing their clinical utility.

  19. A retrospective analysis of survival and prognostic factors of male breast cancer from a single center

    PubMed Central

    2014-01-01

    Background Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. Methods We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients’ OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. Results In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. Conclusions Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease. PMID:24673740

  20. Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer

    PubMed Central

    Zhou, Juan; Yang, Li-Chao; He, Zhen-Yu; Li, Fang-Yan; Wu, San-Gang; Sun, Jia-Yuan

    2015-01-01

    Purpose: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. Methods: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. Results: The median follow-up time was 57 months and the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with blood type A had a poorer 5-year OS than patients with blood type non-A (55.0% vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs. 62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was significantly associated with OS than those with non-A types (hazard ratio (HR) 2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A remained an independent prognostic factor for OS than those with non-A blood types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002). Conclusion: ABO blood group is associated with survival in patients with ovarian cancer, patients with blood type A had a significantly worse OS than patients with non-A blood types, especially in patients with age > 50 years. PMID:26316893

  1. Deletion of 18q is a strong and independent prognostic feature in prostate cancer.

    PubMed

    Kluth, Martina; Graunke, Maximilian; Möller-Koop, Christina; Hube-Magg, Claudia; Minner, Sarah; Michl, Uwe; Graefen, Markus; Huland, Hartwig; Pompe, Raisa; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Lebok, Patrick; Steurer, Stefan; Büscheck, Franziska; Clauditz, Till; Wilczak, Waldemar; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald

    2016-12-27

    Deletion of 18q recurrently occurs in prostate cancer. To evaluate its clinical relevance, dual labeling fluorescence in-situ hybridization (FISH) using probes for 18q21 and centromere 18 was performed on a prostate cancer tissue microarray (TMA). An 18q deletion was found in 517 of 6,881 successfully analyzed cancers (7.5%). 18q deletion was linked to unfavorable tumor phenotype. An 18q deletion was seen in 6.4% of 4,360 pT2, 8.0% of 1,559 pT3a and 11.8% of 930 pT3b-pT4 cancers (P < 0.0001). Deletions of 18q were detected in 6.9% of 1,636 Gleason ≤ 3 + 3, 6.8% of 3,804 Gleason 3 + 4, 10.1% of 1,058 Gleason 4+3, and 9.9% of 344 Gleason ≥ 4 + 4 tumors (P = 0.0013). Deletions of 18q were slightly more frequent in ERG-fusion negative (8.2%) than in ERG-fusion positive cancers (6.4%, P = 0.0063). 18q deletions were also linked to biochemical recurrence (BCR, P < 0.0001). This was independent from established pre- and postoperative prognostic factors (P ≤ 0.0004). In summary, the results of our study identify 18q deletion as an independent prognostic parameter in prostate cancer. As it is easy to measure, 18q deletion may be a suitable component for multiparametric molecular prostate cancer prognosis tests.

  2. PAI-1 -675 4G/5G polymorphism as a prognostic biomarker in breast cancer.

    PubMed

    Lei, Haixin; Hemminki, Kari; Johansson, Robert; Altieri, Andrea; Enquist, Kerstin; Henriksson, Roger; Lenner, Per; Försti, Asta

    2008-05-01

    Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P<0.001), especially in patients with more aggressive tumors. 5G/5G homozygotes were also the group with worse survival among lymph node negative cases. Our finding suggests that genotyping PAI-1 -675 4G/5G may help in clinical prognosis of breast cancer.

  3. Deletion of 18q is a strong and independent prognostic feature in prostate cancer

    PubMed Central

    Möller-Koop, Christina; Hube-Magg, Claudia; Minner, Sarah; Michl, Uwe; Graefen, Markus; Huland, Hartwig; Pompe, Raisa; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Lebok, Patrick; Steurer, Stefan; Büscheck, Franziska; Clauditz, Till; Wilczak, Waldemar; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald

    2016-01-01

    Deletion of 18q recurrently occurs in prostate cancer. To evaluate its clinical relevance, dual labeling fluorescence in-situ hybridization (FISH) using probes for 18q21 and centromere 18 was performed on a prostate cancer tissue microarray (TMA). An 18q deletion was found in 517 of 6,881 successfully analyzed cancers (7.5%). 18q deletion was linked to unfavorable tumor phenotype. An 18q deletion was seen in 6.4% of 4,360 pT2, 8.0% of 1,559 pT3a and 11.8% of 930 pT3b-pT4 cancers (P < 0.0001). Deletions of 18q were detected in 6.9% of 1,636 Gleason ≤ 3 + 3, 6.8% of 3,804 Gleason 3 + 4, 10.1% of 1,058 Gleason 4+3, and 9.9% of 344 Gleason ≥ 4 + 4 tumors (P = 0.0013). Deletions of 18q were slightly more frequent in ERG-fusion negative (8.2%) than in ERG-fusion positive cancers (6.4%, P = 0.0063). 18q deletions were also linked to biochemical recurrence (BCR, P < 0.0001). This was independent from established pre- and postoperative prognostic factors (P ≤ 0.0004). In summary, the results of our study identify 18q deletion as an independent prognostic parameter in prostate cancer. As it is easy to measure, 18q deletion may be a suitable component for multiparametric molecular prostate cancer prognosis tests. PMID:27861151

  4. The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers

    PubMed Central

    Yu, Fei-Yuan; Xu, Qian; Wu, Dan-Dan; Xu, Yan-Ming

    2016-01-01

    Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43–0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42–0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01–0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49–3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48–0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21–0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect

  5. Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer

    PubMed Central

    Cheng, Kai; Liu, Yi-Jun; Xing, Shan; Chi, Pei-dong; Liu, Xiao-Hua; Xue, Ning; Lai, Yan-zhen; Guo, Ling; Zhang, Ge

    2016-01-01

    To evaluate whether serum Cathepsin S (Cat S) could serve as a biomarker for the diagnosis and prognosis of gastric cancer (GC), Enzyme-linked immuno sorbent assay (ELISA) was used to detect serum Cat S in 496 participants including healthy controls and patients with benign gastric diseases, gastric cancer, esophageal cancer, liver cancer, colorectal cancer, nasopharyngeal cancer and lung cancer. The levels of serum Cat S were significantly increased in cancer patients, especially in GC patients. The qRT-PCR, Western blotting, and immunohistochemical staining revealed the overexpression of Cat S in GC cell lines and tissues. The diagnostic value of serum Cat S for GC patients from controls resulted in an AUC of 0.803 with a sensitivity of 60.7% and a specificity of 90.0%. Moreover, the levels of serum Cat S were associated with GC tumor volume, lymphoid nodal status, metastasis status, and stages. Moreover, the patients with high levels of serum Cat S had a poorer overall survival. Univariate analysis revealed Cat S expression was a prognostic factor. The knockdown of Cat S significantly suppressed the migration and invasion of GC cells. This study suggested serum Cat S may be a potential biomarker for the diagnosis and prognosis of GC. PMID:27058412

  6. Forkhead box protein A1 is a prognostic predictor and promotes tumor growth of gastric cancer

    PubMed Central

    Ren, Hongyu; Zhang, Pei; Tang, Yong; Wu, Mengping; Zhang, Weikang

    2015-01-01

    Previous studies have demonstrated the cancer-type specific role of forkhead box protein A1 (FOXA1) in human malignancies. However, the clinical significance of FOXA1 and its biological function in gastric cancer remain unknown. In this study, the expression of FOXA1 in 80 pairs of gastric cancer tissues and corresponding non-tumor tissues was analyzed using immunohistochemistry and quantitative real-time polymerase chain reaction. We found that the levels of FOXA1 protein and mRNA in gastric cancer tissues were significantly higher than those in matched tumor-adjacent tissues. Furthermore, clinical association analysis indicated that the positive expression of FOXA1 was associated with adverse clinicopathological characteristics of gastric cancer patients including poor tumor differentiation, large tumor size, and advanced tumor-node-metastasis tumor stage. Notably, gastric cancer patients with positive expression of FOXA1 had a poorer 5-year overall survival and recurrence-free survival. In addition, FOXA1 knockdown remarkably inhibited cell proliferation and induced apoptosis in both SGC-7901 and MGC-803 cells. In vivo studies indicated that FOXA1 knockdown prominently suppressed tumor growth of gastric cancer in a nude mouse xenograft model. Mechanistically, we disclosed that the expression of Yes-associated protein was decreased accordingly after FOXA1 knockdown in both SGC-7901 and MGC-803 cells. Taken together, our data suggest that FOXA1 may serve as a promising prognostic indicator and an attractive therapeutic target of gastric cancer. PMID:26527889

  7. Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study

    PubMed Central

    Zhao, Yi-Xuan; Liu, Shuang; Hu, Yan-Bing; Ge, Yan-Yan; Lv, Dong-Mei

    2017-01-01

    This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time–intensity curves (TICs) were obtained. Hematoxylin–eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER), c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI), relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors. CEUS is a useful tool for the early diagnosis and prognosis of breast cancer. PMID:28260926

  8. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

  9. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

    PubMed Central

    Weixler, Benjamin; Cremonesi, Eleonora; Sorge, Roberto; Muraro, Manuele Giuseppe; Delko, Tarik; Nebiker, Christian A.; Däster, Silvio; Governa, Valeria; Amicarella, Francesca; Soysal, Savas D.; Kettelhack, Christoph; von Holzen, Urs W.; Eppenberger-Castori, Serenella; Spagnoli, Giulio C.; Oertli, Daniel; Iezzi, Giandomenica; Terracciano, Luigi; Tornillo, Luigi

    2015-01-01

    Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers. PMID:26439988

  10. Prognostic factors in male breast cancer: a population-based study.

    PubMed

    Leone, José Pablo; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Julieta; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Bhargava, Rohit

    2016-04-01

    Prognostic factors in male breast cancer (MaBC) are controversial. The objective of this study was to analyze patient characteristics and prognostic factors in MaBC over the last decade. Using the Surveillance, Epidemiology, and End Results program, we extracted MaBC patients diagnosed between 2003 and 2012. Patient characteristics were compared between tumor grades. We conducted univariate and multivariate analyses to determine the effects of each prognostic variable on overall survival (OS). The study included 2992 patients. The majority had ductal (85 %), ER-positive (95.1 %), and PR-positive (86 %) breast cancer; however, only 12.4 % had grade I tumors. Stage I and II disease represented 73 % of cases. There was a significant association between grade III/IV tumors with ductal histology, ER and PR negativity, advanced stage, receipt of mastectomy and radiotherapy, and breast cancer death (all P < 0.05). ER-positive patients had better OS (hazard ratio 0.69, P = 0.03); however, after 7.5 years, OS rates by ER status were similar. In multivariate analysis, older age, grade III/IV tumors, stage IV disease, no surgery, no radiotherapy, ER-negative tumors, and unmarried patients had significantly shorter OS (all P < 0.05). Over the past decade, MaBC has been diagnosed most frequently with early stages of disease and high rates of ER positivity; however, grade I is uncommon. ER positivity is associated with better prognosis, mainly during the first 5 years after diagnosis. Age at diagnosis, tumor grade, stage, surgery, radiotherapy, ER, and marital status have clear impact on OS in MaBC.

  11. PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy

    PubMed Central

    Yan, Dongwang; Cui, Feifei; Wang, Xiaoliang; Yu, Fudong; Xue, Yingming; Feng, Xiaodong; Wang, Jingtao; Wang, Xiao; Jiang, Tao; Zhang, Meng; Zhao, Senlin; Yu, Yang; Tang, Huamei; Peng, Zhihai

    2015-01-01

    p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer. PMID:25426562

  12. Assessment, treatment, and prognostic implications of CAD in patients undergoing TAVI.

    PubMed

    Danson, Edward; Hansen, Peter; Sen, Sayan; Davies, Justin; Meredith, Ian; Bhindi, Ravinay

    2016-05-01

    Coronary artery disease (CAD) is common in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), but its clinical relevance is controversial. At present, the optimal means of defining CAD in patients undergoing TAVI with respect to its prognostic implications and the assessment of myocardial ischaemia is not known. For this reason, the best treatment options are a matter for debate, and current guidelines do not recommend revascularization. As the indications for TAVI expand, the lack of any rigorous means of guiding coronary revascularization might negatively affect the clinical outcomes of future patients. In this Review, we summarize the methods of assessing CAD in TAVI populations, and the data on the safety and efficacy of percutaneous coronary intervention in patients undergoing TAVI. We discuss the putative effects of aortic stenosis on the functional assessment of CAD using pressure or flow wires or by noninvasive stress testing. We propose that a new, well-validated method of assessing CAD as a cause of myocardial ischaemia--which distinguishes it from myocardial infarction, previous revascularization, or non-flow-limiting disease--in patients with severe aortic stenosis is needed to guide revascularization in the current era of TAVI.

  13. The importance of postoperative quality of recovery: influences, assessment, and clinical and prognostic implications.

    PubMed

    Bowyer, Andrea; Royse, Colin

    2016-02-01

    Quality of recovery is a complex construct whose definition is influenced heavily by the opinions and biases of the individual patient, clinician, or institution. Asa result, recovery assessment tools differ in their fundamental definitions of recovery, breadth, and assessment time frame. Accurate assessment of recovery is essential as suboptimal recovery has both economic and prognostic implications. Quality of care is often substituted as a surrogate at the institutional level for quality of recovery, but it is ideologically distinct from patients' perceived quality of care, recovery, and satisfaction. Recovery tools also differ in their assessment of recovery as a continuous vs dichotomous variable and in their focus at the group vs individual level. Ideally, recovery measures should assess outcomes in a simple dichotomous fashion and maintain relevancy by assessing in multiple domains at various time points. Assessment of recovery in a dichotomous fashion also has both clinical and research applications. It allows identification of suboptimal recovery at both individual and group levels,respectively, and when performed in real time, it allows the opportunity for timely targeted intervention specific to individual patients as well as for resource rationalization.

  14. P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients

    PubMed Central

    Pan, Yunbao; Yuan, Yufen; Liu, Guoshi; Wei, Yongchang

    2017-01-01

    Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC. PMID:28235003

  15. Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers: a meta-analysis

    PubMed Central

    Yang, Hong-Bo; Xing, Meng; Ma, Lei-Na; Feng, Ling-Xin; Yu, Zhuang

    2016-01-01

    Setting For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet–lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. Objective To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. Design We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. Results Both high NLR (P < 0.00001) and high PLR (P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS (P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, (P = 0.006) extensive lymph nodetastasis(N2–3) (P = 0.01), poor differentiation (P = 0.0002) and vascular invasion(P = 0.002). There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. Conclusions We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes. PMID:27732958

  16. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer*

    PubMed Central

    Zhao, Changqing; Annamalai, Loganath; Guo, Changfa; Kothandaraman, Narasimhan; Koh, Stephen Chee Liang; Zhang, Huoming; Biswas, Arijit; Choolani, Mahesh

    2007-01-01

    Abstract OBJECTIVE This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer. PMID:17325738

  17. The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer.

    PubMed

    Lee, Sang Hoon; Chung, Moon Jae; Kim, Bun; Lee, Hee Seung; Lee, Hyun Jik; Heo, Ja Yoon; Kim, Yeong Jin; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

    2017-04-01

    Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm(3)) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).

  18. Correlation between molybdenum target mammography signs and pathological prognostic factors of breast cancer.

    PubMed

    Zhang, Y; Ma, A D; Jia, H X

    2016-01-01

    This study explores the correlation between molybdenum target (mo-target) mammography signs and pathological prognostic factors of breast cancer. We selected 320 breast cancer patients who were treated between January 2014 and January 2016; using single-factor and multiple-factor logistic regression method, we made correlation analysis on their clinical features, pathological features and mo-target mammography signs. Among mo-target mammography signs, lumps accompanied with calcification and blurry edge were associated with high histologic grades; lumps accompanied with calcification and clear edge were associated with Ki-67 positive; compared with the patients who had lumps with non-stellate edges, positive rates of estrogen receptor (ER) and progesterone receptor (PR) were significantly higher for the patients who had lumps with stellate edges (p < 0.01), while positive rate of human epidermal growth factor receptor-2 (HER-2) and tumor proliferative activity were significantly lower (p < 0.05, p < 0.01). According to the study, we can conclude that mo-target mammography signs mainly include lumps and calcification. Mo-target mammography can improve the accuracy of diagnosis and reduce misdiagnosis or missed diagnosis. Part of mo-target mammography signs are associated with clinical pathology prognostic factors; by grasping the relation, breast cancer patient conditions are expected to be relieved.

  19. Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer

    PubMed Central

    Keller, Xavier Etienne; Kardas, Piotr; Acevedo, Claudio; Sais, Giovanni; Poyet, Cédric; Banzola, Irina; Mortezavi, Ashkan; Seifert, Burkhardt; Sulser, Tullio

    2015-01-01

    Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as important inflammatory pathogens in prostate cancer. Here, we evaluated whether the preoperative antibody response to BKPyV large T antigen (LTag) and viral capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in 226 patients undergoing radical prostatectomy for primary prostate cancer. Essentially, the multivariate Cox regression analysis revealed that preoperative seropositivity to BKPyV LTag significantly reduced the risk of biochemical recurrence, independently of established predictors of biochemical recurrence such as tumor stage, Gleason score and surgical margin status. The predictive accuracy of the regression model was denotatively increased by the inclusion of the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine gene expression profile upon assessment of the cellular immune response elicited by LTag. Taken together, our findings suggest that the BKPyV LTag serology may serve as a prognostic factor in prostate cancer. If validated in additional studies, this biomarker may allow for better treatment decisions after radical prostatectomy. Finally, the favorable outcome of LTag seropositive patients may provide a potential opportunity for novel therapeutic approaches targeting a viral antigen. PMID:25749042

  20. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  1. Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer

    PubMed Central

    Gu, Xiaobin; Gao, Xian-Shu; Cui, Ming; Xie, Mu; Peng, Chuan; Bai, Yun; Guo, Wei; Han, Linjun; Gu, Xiaodong; Xiong, Wei

    2016-01-01

    The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; I2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88–2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC. PMID:27409665

  2. Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications.

    PubMed

    Pinheiro, Danilo do Rosário; Ferreira, Wallax Augusto Silva; Barros, Mariceli Baia Leão; Araújo, Mariana Diniz; Rodrigues-Antunes, Symara; Borges, Bárbara do Nascimento

    2014-09-07

    Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice. In this sense, we observed that the use of genetic markers, especially mutations and polymorphisms, should be carefully considered, as they are strongly affected by ethnicity. Proteomic-based markers show promise, but the higher costs of the associated techniques continue to make this approach expensive for routine use. Alternatively, epigenetic markers appear to be very promising, as they can be detected in bodily fluids as well as tissues. However, such markers must be used carefully because epigenetic changes may occur due to environmental factors and aging. Despite the advances in technology and its access, to date, there are few defined biomarkers of prognostic and diagnostic use for gastric tumors. Therefore, the use of a panel of several approaches (genetic, epigenetic and proteomic) should be considered the best alternative for clinical practice.

  3. TTK is a favorable prognostic biomarker for triple-negative breast cancer survival

    PubMed Central

    Xu, Qianqian; Xu, Yali; Pan, Bo; Wu, Liangcai; Ren, Xinyu; Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Shen, Songjie; Zhang, Xiaohui; Wang, Changjun; Zhong, Ying; Zhou, Liangrui; Liang, Zhiyong; Zhao, Haitao; Sun, Qiang

    2016-01-01

    Purpose Previous studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC. Results Of 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5.9% displayed whole cell immunostaining. At a discriminating threshold of 55, elevated TTK expression was associated with prolonged disease free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.024) in primary TNBC and prolonged DFS in individual basal-like (p = 0.001) and non-basal-like (p = 0.001) TNBC subtypes. In addition, Cox regression analysis demonstrated that elevated TTK expression was an independent prognostic factor for DFS in TNBC (p < 0.001). Methods TTK expression of 169 samples was tested by immunohistochemistry (IHC). A receiver operating characteristic (ROC) curve was used to identify a cutpoint for TTK expression, which was analyzed for its association with patients' clinicopathological factors and survival using Chi-square, log-rank, and Cox regression analyses. Conclusions TTK is a favorable prognostic biomarker associated with TNBC survival. PMID:27833085

  4. Interleukin 6 Receptor Is an Independent Prognostic Factor and a Potential Therapeutic Target of Ovarian Cancer

    PubMed Central

    Isobe, Aki; Sawada, Kenjiro; Kinose, Yasuto; Ohyagi-Hara, Chifumi; Nakatsuka, Erika; Makino, Hiroshi; Ogura, Tomonori; Mizuno, Tomoko; Suzuki, Noriko; Morii, Eiichi; Nakamura, Koji; Sawada, Ikuko; Toda, Aska; Hashimoto, Kae; Mabuchi, Seiji; Ohta, Tsuyoshi; Morishige, Ken-ichirou; Kurachi, Hirohisa; Kimura, Tadashi

    2015-01-01

    Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment. PMID:25658637

  5. Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

    PubMed Central

    Lo Nigro, Cristiana; Ricci, Vincenzo; Vivenza, Daniela; Granetto, Cristina; Fabozzi, Teresa; Miraglio, Emanuela; Merlano, Marco C

    2016-01-01

    AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling. METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion. RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The prognostic value of selected microRNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial. CONCLUSION: This review focuses on the personalized treatment of mCRC and discusses the

  6. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  7. Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Willis, Scooter; Villalobos, Victor M.; Gevaert, Olivier; Abramovitz, Mark; Williams, Casey; Sikic, Branimir I.; Leyland-Jones, Brian

    2016-01-01

    Purpose To discover novel prognostic biomarkers in ovarian serous carcinomas. Methods A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer’s method and selected for statistical significance with a false discovery rate (FDR) <.05 using the Benjamini-Hochberg method. Results Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82). Conclusion A meta-analysis of all single genes identified thirty-two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi-gene signature and tested in future ovarian cohorts. PMID:26886260

  8. Evolving transcriptomic fingerprint based on genome‐wide data as prognostic tools in prostate cancer

    PubMed Central

    Schliekelman, Mark; Shin, Heesun; Erho, Nicholas; Davicioni, Elai

    2015-01-01

    Background Information Prostate cancer (PCa) is a common disease but only a small subset of patients are at risk of developing metastasis and lethal disease, and identifying which patients will progress is challenging because of the heterogeneity underlying tumour progression. Understanding this heterogeneity at the molecular level and the resulting clinical impact is a critical step necessary for risk stratification. Defining genomic fingerprint elucidates molecular variation and may improve PCa risk stratification, providing more accurate prognostic information of tumour aggressiveness (or lethality) for prognostic biomarker development. Therefore, we explored transcriptomic differences between patients with indolent disease outcome and patients who developed metastasis post‐radical prostatectomy using genome‐wide expression data in the post radical prostatectomy clinical space before metastatic spread. Results Based on differential expression analysis, patients with adverse pathological findings who are at higher risk of developing metastasis have a distinct transcriptomic fingerprint that can be detected on surgically removed prostate specimens several years before metastasis detection. Nearly half of the transcriptomic fingerprint features were non‐coding RNA highlighting their pivotal role in PCa progression. Protein‐coding RNA features in the fingerprint are involved in multiple pathways including cell cycle, chromosome structure maintenance and cytoskeleton organisation. The metastatic transcriptomic fingerprint was determined in independent cohorts verifying the association between the fingerprint and metastatic patients. Further, the fingerprint was confirmed in metastasis lesions demonstrating that the fingerprint represents early metastatic transcriptomic changes, suggesting its utility as a prognostic tool to predict metastasis and provide clinical value in the early radical prostatectomy setting. Conclusions Here, we show that transcriptomic

  9. Integrative Protein-Based Prognostic Model for Early Stage Endometrioid Endometrial Cancer

    PubMed Central

    Yang, Ji-Yeon; Werner, Henrica M.J.; Li, Jie; Westin, Shannon N.; Lu, Yiling; Halle, Mari K.; Trovik, Jone; Salvesen, Helga B.; Mills, Gordon B.; Liang, Han

    2015-01-01

    Purpose Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design We employed two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test p-value = 0.565 for disease stage, 0.567 for tumor grade, 1.3×10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. PMID:26224872

  10. 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

  11. Impaired SNX9 Expression in Immune Cells during Chronic Inflammation: Prognostic and Diagnostic Implications.

    PubMed

    Ish-Shalom, Eliran; Meirow, Yaron; Sade-Feldman, Moshe; Kanterman, Julia; Wang, Lynn; Mizrahi, Olga; Klieger, Yair; Baniyash, Michal

    2016-01-01

    Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition. We found that myeloid-derived suppressor cells, which are elevated in the course of chronic inflammation, are responsible for the observed SNX9 reduced expression. Moreover, SNX9 downregulation is reversible, as its expression levels return to normal and immune functions are restored when the inflammatory response and/or myeloid-derived suppressor cells are neutralized. SNX9 downregulation was detected in numerous mouse models for pathologies characterized by chronic inflammation such as chronic infection (Leishmania donovani), cancer (melanoma and colorectal carcinoma), and an autoimmune disease (rheumatoid arthritis). Interestingly, reduced levels of SNX9 were also observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host's immune status and inflammatory stage. Our new discovery of SNX9 as being regulated by chronic inflammation and its association with immunosuppression, in addition to the CD247 regulation under such conditions, show the global impact of chronic inflammation and the generated immune environment on different cellular pathways in a diverse spectrum of diseases.

  12. Histone demethylase GASC1 - a potential prognostic and predictive marker in invasive breast cancer

    PubMed Central

    2012-01-01

    Background The histone demethylase GASC1 (JMJD2C) is an epigenetic factor suspected of involvement in development of different cancers, including breast cancer. It is thought to be overexpressed in the more aggressive breast cancer types based on mRNA expression studies on cell lines and meta analysis of human breast cancer sets. This study aimed to evaluate the prognostic and predictive value of GASC1 for women with invasive breast cancer. Methods All the 355 cases were selected from a cohort enrolled in the Kuopio Breast Cancer Project between April 1990 and December 1995. The expression of GASC1 was studied by immunohistochemistry (IHC) on tissue microarrays. Additionally relative GASC1 mRNA expression was measured from available 57 cases. Results In our material, 56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with GASC1 negative tumors had two years shorter breast cancer specific survival and time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034 respectively). The majority of GASC1 negative tumors were ductal cases (72%) of higher histological grade (84% of grade II and III altogether). When we evaluated estrogen receptor negative and progesterone receptor negative cases separately, there was 2 times more GASC1 negative than GASC1 positive tumors in each group (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3 times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49, p=0.007 and HR=0.33, p=0.015, respectively). The expression of GASC1 mRNA was in agreement with the protein analysis. Conclusions This study indicates that the GASC1 is both a prognostic and a predictive factor for women with invasive breast cancer. GASC1 negativity is associated with tumors of more aggressive histopathological

  13. Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis

    PubMed Central

    Cao, Hanyu; Wang, Si; Zhang, Zhenyu; Lou, Jiangyan

    2016-01-01

    Objective This study aimed to examine the prognostic value of overexpressed p16INK4a in vulvar cancer. Although the tumor suppressor p16INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear. Methods All publications in English language on the association between p16INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios(ORs) or risk ratios(RRs) with 95% confidence intervals(CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger’s regression test. Results A total of 17 studies with 2309 patients were included. The p16INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage(I+II vs III+IV; OR = 0.60,95%CI:0.41–0.86,P = 0.006),negative lymph node metastasis(negative vs positive; OR = 0.61,95%CI:0.39–0.95,P = 0.029),patient’s age<55(OR = 0.54,95%CI:0.31–0.96,P = 0.034),human papillomavirus–positive status(OR = 0.01,95%CI:0.00–0.11,P<0.001),and higher overall survival(RR = 0.53,95%CI = 0.35–0.80,P = 0.003). Conclusion The p16INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer. PMID:27031618

  14. Prognostic Factors for Node-Negative Advanced Gastric Cancer after Curative Gastrectomy

    PubMed Central

    Lee, Eun Woo; Koo, Ho-Seok

    2016-01-01

    Purpose Lymph node (LN) metastasis is the best prognostic indicator in non-distant metastatic advanced gastric cancer. This study aimed to assess the prognostic value of various clinicopathologic factors in node-negative advanced gastric cancer. Materials and Methods We retrospectively analyzed the clinical records of 254 patients with primary node-negative stage T2~4 gastric cancer. These patients were selected from a pool of 1,890 patients who underwent radical resection at Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University Seoul Paik Hospital between 1998 and 2008. Results Of the 254 patients, 128 patients (50.4%), 88 patients (34.6%), 37 patients (14.6%), and 1 patient (0.4%) had T2, T3, T4a, and T4b tumors, respectively. In a univariate analysis, operation type, T-stage, venous invasion, tumor size, and less than 15 LNs significantly correlated with tumor recurrence and cumulative overall survival. In a multivariate logistic regression analysis, tumor size, venous invasion, and less than 15 LNs significantly and independently correlated with recurrence. In a multivariate Cox proportional hazards analysis, tumor size (hazard ratio [HR]: 2.926; 95% confidence interval [CI]: 1.173~7.300; P=0.021), venous invasion (HR: 3.985; 95% CI: 1.401~11.338; P=0.010), and less than 15 LNs (HR: 0.092; 95% CI: 0.029~0.290; P<0.001) significantly correlated with overall survival. Conclusions Node-negative gastric cancers recurred in 8.3% of the patients in our study. Tumor size, venous invasion, and less than 15 LNs reliably predicted recurrence as well as survival. Aggressive postoperative treatments and timely follow-ups should be considered in cases with these characteristics. PMID:27752393

  15. Radiomic feature clusters and Prognostic Signatures specific for Lung and Head & Neck cancer

    PubMed Central

    Parmar, Chintan; Leijenaar, Ralph T. H.; Grossmann, Patrick; Rios Velazquez, Emmanuel; Bussink, Johan; Rietveld, Derek; Rietbergen, Michelle M.; Haibe-Kains, Benjamin; Lambin, Philippe; Aerts, Hugo J.W.L.

    2015-01-01

    Radiomics provides a comprehensive quantification of tumor phenotypes by extracting and mining large number of quantitative image features. To reduce the redundancy and compare the prognostic characteristics of radiomic features across cancer types, we investigated cancer-specific radiomic feature clusters in four independent Lung and Head & Neck (H∓N) cancer cohorts (in total 878 patients). Radiomic features were extracted from the pre-treatment computed tomography (CT) images. Consensus clustering resulted in eleven and thirteen stable radiomic feature clusters for Lung and H & N cancer, respectively. These clusters were validated in independent external validation cohorts using rand statistic (Lung RS = 0.92, p < 0.001, H & N RS = 0.92, p < 0.001). Our analysis indicated both common as well as cancer-specific clustering and clinical associations of radiomic features. Strongest associations with clinical parameters: Prognosis Lung CI = 0.60 ± 0.01, Prognosis H & N CI = 0.68 ± 0.01; Lung histology AUC = 0.56 ± 0.03, Lung stage AUC = 0.61 ± 0.01, H & N HPV AUC = 0.58 ± 0.03, H & N stage AUC = 0.77 ± 0.02. Full utilization of these cancer-specific characteristics of image features may further improve radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor phenotypic characteristics in clinical practice. PMID:26251068

  16. Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer.

    PubMed

    Corda, Gabriele; Sala, Gianluca; Lattanzio, Rossano; Iezzi, Manuela; Sallese, Michele; Fragassi, Giorgia; Lamolinara, Alessia; Mirza, Hasan; Barcaroli, Daniela; Ermler, Sibylle; Silva, Elisabete; Yasaei, Hemad; Newbold, Robert F; Vagnarelli, Paola; Mottolese, Marcella; Natali, Pier Giorgio; Perracchio, Letizia; Quist, Jelmar; Grigoriadis, Anita; Marra, Pierfrancesco; Tutt, Andrew N; Piantelli, Mauro; Iacobelli, Stefano; De Laurenzi, Vincenzo; Sala, Arturo

    2017-02-01

    Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, and is often deregulated in cancer. In this study, we found that the gene encoding the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple-negative breast cancer (TNBC) subtype. Ablation of FZD6 expression in mammary cancer cell lines: (1) inhibited motility and invasion; (2) induced a more symmetrical shape of organoid three-dimensional cultures; and (3) inhibited bone and liver metastasis in vivo. Mechanistically, FZD6 signalling is required for the assembly of the fibronectin matrix, interfering with the organization of the actin cytoskeleton. Ectopic delivery of fibronectin in FZD6-depleted, triple-negative MDA-MB-231 cells rearranged the actin cytoskeleton and restored epidermal growth factor-mediated invasion. In patients with localized, lymph node-negative (early) breast cancer, positivity of tumour cells for FZD6 protein identified patients with reduced distant relapse-free survival. Multivariate analysis indicated an independent prognostic significance of FZD6 expression in TNBC tumours, predicting distant, but not local, relapse. We conclude that the FZD6-fibronectin actin axis identified in our study could be exploited for drug development in highly metastatic forms of breast cancer, such as TNBC. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  17. Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer.

    PubMed Central

    Crawford, R. A.; Caldwell, C.; Iles, R. K.; Lowe, D.; Shepherd, J. H.; Chard, T.

    1998-01-01

    bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis. PMID:9683295

  18. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

    PubMed Central

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-01-01

    Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set. PMID:26384309

  19. Evaluation of the prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers

    PubMed Central

    Tian, Tian; Ruan, Miao; Yang, Wentao; Shui, Ruohong

    2016-01-01

    Tumor-infiltrating lymphocytes (TILs) may be associated with clinical outcome in triple-negative breast cancers (TNBCs). However, lacking of standardized methodologies in TILs evaluation has hindered its application in clinical practice. To evaluate the prognostic role of TILs scored by methods recommended by International TILs Working Group 2014, we performed a retrospective study of TILs in 425 primary invasive TNBCs in a Chinese population with a median follow-up of 4 years. Intratumoral TILs (iTILs) and stromal TILs (sTILs) were scored respectively. The associations between TILs and disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were evaluated with COX models. ITILs were not associated with prognosis. Higher sTILs were associated with better prognosis; for every 10% increase in sTILs, a 5% reduction of risk of recurrence or death (P < 0.001), 5% reduction of risk of distant recurrence (P < 0.001), and 4% reduction of risk of death (P = 0.002) were observed. Multivariate analysis confirmed sTILs to be an independent prognostic marker. 3.5% of TNBCs had more than 50% lymphocytes (lymphocyte-predominant breast cancer, LPBC), and associations between LPBC status and prognosis were observed but did not reach statistical significance. TNBCs with more than 20% sTILs had a significantly better prognosis than the patients with no more than 20% sTILs. In conclusion, our study indicated that sTILs scored by methods recommended by International TILs Working Group 2014 were associated with the prognosis of TNBCs. STILs could be an independent prognostic biomarker in TNBCs, increasing sTILs predicting better prognosis. PMID:27323808

  20. Prognostic comparison of the proliferation markers (mitotic activity index, phosphohistone H3, Ki67), steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T₁₋₂N₀M₀ breast cancer.

    PubMed

    Gudlaugsson, Einar; Klos, Jan; Skaland, Ivar; Janssen, Emiel A M; Smaaland, Rune; Feng, Weiwei; Shao, Zhimin; Malpica, Anais; Baak, Jan P A

    2013-04-01

    The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T₁₋₂N₀M₀ breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.

  1. Breast cancer. Part 3: advanced cancer and psychological implications.

    PubMed

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  2. Prognostic significance of Notch ligands in patients with non-small cell lung cancer.

    PubMed

    Pancewicz-Wojtkiewicz, Joanna; Eljaszewicz, Andrzej; Kowalczuk, Oksana; Niklinska, Wieslawa; Charkiewicz, Radoslaw; Kozłowski, Miroslaw; Miasko, Agnieszka; Moniuszko, Marcin

    2017-01-01

    The Notch signaling pathway is deregulated in numerous solid types of cancer including non-small cell lung cancer (NSCLC). However, the profile of Notch ligand expression remains unclear. Therefore, the present study aimed to determine the profile of Notch ligands in NSCLC patients and to investigate whether quantitative assessment of Notch ligand expression may have prognostic significance in NSCLC patients. The study was performed in 61 pairs of tumor and matched unaffected lung tissue specimens obtained from patients with various stages of NSCLC, which were analyzed by reverse transcription-polymerase chain reaction. The marked expression levels of certain analyzed genes were detected in NSCLC samples and in noncancerous lung samples. Of the five Notch ligands, jagged 1 (Jag1), jagged 2, delta-like protein 1 and delta-like protein 4 were expressed in the majority of tissues, but their expression levels were reduced in NSCLC when compared with noncancerous lung tissue (P<0.001). Delta-like protein 3 expression was consistently low and was observed only in 21/61 tumor tissue samples. Taken together, Notch ligands are expressed in NSCLC. However, the expression level is reduced when compared to noncancerous tissue. Furthermore, the present study revealed that quantitative assessment of Jag1 expression in NSCLC may improve prognostication of patient survival.

  3. Urinary cell microRNA-based prognostic classifier for non-muscle invasive bladder cancer.

    PubMed

    Ingelmo-Torres, Mercedes; Lozano, Juan José; Izquierdo, Laura; Carrion, Albert; Costa, Meritxell; Gómez, Lidia; Ribal, María José; Alcaraz, Antonio; Mengual, Lourdes

    2017-02-14

    Current prognostic tools for non-muscle invasive bladder cancer (NMIBC) do not have enough discriminative capacity to predict the risk of tumour progression. This study aimed to identify urinary cell microRNAs that may be useful as non-invasive predictive biomarkers of tumour progression in NMIBC patients. To this end, 210 urine samples from NMIBC patients were included in the study. RNA was extracted from urinary cells and expression of 8 microRNAs, previously described by our group, was analysed by quantitative PCR. A tumour progression predicting model was developed by Cox regression analysis and validated by bootstrapping. Regression analysis identified miR-140-5p and miR-92a-3p as independent predictors of tumour progression. The risk score derived from the model containing these two microRNAs was able to discriminate between two groups with a highly significant different probability of tumour progression (HR, 5.204; p<0.001) which was maintained when patients were stratified according to tumour risk. The algorithm was also able to identify two groups with different cancer-specific survival (HR, 3.879; p=0.021). Although the data needs to be externally validated, miRNA analysis in urine appears to be a valuable prognostic tool in NMIBC patients.

  4. Capacitance of Membrane As a Prognostic Indicator of Survival in Head and Neck Cancer

    PubMed Central

    Małecka-Massalska, Teresa; Mlak, Radosław; Smoleń, Agata; Brzozowska, Anna; Surtel, Wojciech; Morshed, Kamal

    2016-01-01

    Background Evaluation of prognostic value of capacitance of membrane (Cm), parameter measured by bioelectrical impedance (BIA) as an alternative to known clinical factors in patients with Head and Neck Cancer (HNC). Methods A cohort of 75 stage IIIB and IV HNC patients treated in Department of Otolaryngology, Head and Neck Surgery, Medical University of Lublin, Poland were prospectively evaluated. Cm measurements were performed in all patients using a bioelectrical impedance analyzer that was set on a frequency of 50 kHz. Results of Cm measurements were presented in nF. Survival differences were estimated using Kaplan–Meier method. Results Significantly higher Cm median was noted in well-nourished(n = 45) compared to malnourished (n = 30) patients (1.41 vs 1.01 respectively; p = 0.0009). Established in ROC curves analysis cut-off value (0.743) was characterized by 98% specificity and 37% sensitivity in the detection of malnutrition. Median overall survival (mOS) in the cohort was 32months. At the time of analysis deaths were recorded in 47 cases (62.7%). In patients who had Cm below the level of 0.743 risk of OS shortening was significantly higher than in other patients (12.1 and 43.4 months respectively; HR = 8.47, 95%CI: 2.91–24.66; χ2 = 15.38, p = 0.0001). Conclusion Cm is a strong, independent prognostic factor in head and neck cancer. PMID:27802349

  5. SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer

    PubMed Central

    Sun, Hui-Min; Mi, Yu-Shuai; Yu, Fu-Dong; Han, Yang; Liu, Xi-Sheng; Lu, Su; Zhang, Yu; Zhao, Sen-Lin; Ye, Ling; Liu, Ting-Ting; Yang, Dao-Hua; Sun, Xiao-Feng; Qin, Xue-Bin; Zhou, Zong-Guang; Tang, Hua-Mei; Peng, Zhi-Hai

    2016-01-01

    Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC. PMID:27648355

  6. Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Ban, Wooho; Lee, Jong Min; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyeon Hui; Rhee, Chin Kook; Moon, Hwa Sik

    2016-01-01

    Purpose To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). Materials and Methods From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. Results In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. Conclusion Dyspnea could be a significant prognostic factor in patients with NSCLC. PMID:27401635

  7. The prognostic relevance of the mitotic activity index in axillary lymph node-negative breast cancer.

    PubMed

    Jobsen, Jan J; van der Palen, Job; Brinkhuis, Mariël; Nortier, Johan W R; Struikmans, Henk

    2015-01-01

    The aim of the present study is to look at the mitotic activity index (MAI) as a prognostic factor in a prospective population-based cohort of lymph node-negative invasive breast cancer patients. Analyses were based on 2,048 breast-conserving therapies in 1,971 patients, node-negative, and without any form of adjuvant systemic therapy with long-term follow-up. The 15-year distant metastases-free survival (DMFS) for women ≤55 years was 88.3 % for low MAI values (≤12) versus 73.4 % for high MAI values (>12); (HR 2.8; 95 % CI 1.8-4.4; p < 0.001). Multivariate analyses for DMFS showed significance for MAI. For MAI and Bloom-Richardson grading, by performing a likelihood ratio test, we showed the statistical significance for both. For women >55-years, the MAI was not an independent significant factor. We also confirmed the above findings for disease-specific survival. When multi-gene assays are not available, the MAI remains a robust prognostic marker in women younger than 55 years of age with early node-negative breast cancer.

  8. MicroRNA-222 expression and its prognostic potential in non-small cell lung cancer.

    PubMed

    Mao, Kai-ping; Zhang, Wei-na; Liang, Xiao-min; Ma, Yu-rong

    2014-01-01

    Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox's proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention.

  9. A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

    PubMed Central

    Schell, Michael J.; Yang, Mingli; Teer, Jamie K.; Lo, Fang Yin; Madan, Anup; Coppola, Domenico; Monteiro, Alvaro N. A.; Nebozhyn, Michael V.; Yue, Binglin; Loboda, Andrey; Bien-Willner, Gabriel A.; Greenawalt, Danielle M.; Yeatman, Timothy J.

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC. PMID:27302369

  10. ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.

    PubMed

    Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang-Gu; An, Sungkwan; Han, Young-Hoon; Kim, Jae-Sung

    2015-02-20

    Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.

  11. Functional imaging for prostate cancer: therapeutic implications.

    PubMed

    Mari Aparici, Carina; Seo, Youngho

    2012-09-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities computed tomography (CT) or magnetic resonance imaging (single photon emission computed tomography [SPECT]/CT, positron emission tomography [PET]/CT, and PET/magnetic resonance imaging), are promising tools for the management of prostate cancer, particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regard to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, although the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging, including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects.

  12. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

    PubMed

    Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott C; Chasseing, Norma Alejandra

    2016-10-01

    Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

  13. The risk factors and prognostic implication of acute pulmonary edema in resuscitated cardiac arrest patients

    PubMed Central

    Kang, Dae-hyun; Kim, Joonghee; Rhee, Joong Eui; Kim, Taeyun; Kim, Kyuseok; Jo, You Hwan; Lee, Jin Hee; Lee, Jae Hyuk; Kim, Yu Jin; Hwang, Seung Sik

    2015-01-01

    Objective Pulmonary edema is frequently observed after a successful resuscitation in out-of-hospital cardiac arrest (OHCA) patients. Currently, its risk factors and prognostic implications are mostly unknown. Methods Adult OHCA patients with a presumed cardiac etiology who achieved sustained return of spontaneous circulation (ROSC) in emergency department were retrospectively analyzed. The patients were grouped according to the severity of consolidation on their initial chest X-ray (group I, no consolidation; group II, patchy consolidations; group III, consolidation involving an entire lobe; group IV, total white-out of any lung). The primary objective was to identify the risk factors of developing severe pulmonary edema (group III or IV). The secondary objective was to evaluate the association between long-term prognosis and the severity of pulmonary edema. Results One hundred and seven patients were included. Total duration of cardiopulmonary resuscitation (CPR) and initial pCO2 level were both independent predictors of developing severe pulmonary edema with their odds ratio (OR) being 1.02 (95% confidence interval [CI], 1.00 to 1.04; per 1 minute) and 1.04 (95% CI, 1.01 to 1.07; per 1 mmHg), respectively. The long term prognosis was significantly poor in patients with severe pulmonary edema with a OR for good outcome (6-month cerebral performance category 1 or 2) being 0.22 (95% CI, 0.06 to 0.79) in group III and 0.16 (95% CI, 0.04 to 0.63) in group IV compared to group I. Conclusion The duration of CPR and initial pCO2 level were both independent predictors for the development of severe pulmonary edema after resuscitation in emergency department. The severity of the pulmonary edema was significantly associated with long-term outcome. PMID:27752581

  14. Multifocal and multicentric glioblastoma: Improved characterisation with FLAIR imaging and prognostic implications.

    PubMed

    Lasocki, Arian; Gaillard, Frank; Tacey, Mark; Drummond, Katharine; Stuckey, Stephen

    2016-09-01

    Glioblastoma usually presents on imaging as a single peripherally enhancing lesion, but multiple enhancing lesions can occur, termed multifocal if there is a connection between enhancing lesions, or multicentric when no communication is demonstrated. We aim to determine the incidence and prognostic implications of multifocal and multicentric glioblastoma in the era of modern MRI, focusing on the added benefit of T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging. Patients with a new diagnosis of glioblastoma were identified. Preoperative MRI were reviewed to determine whether more than one distinct enhancing lesion was present, and whether there was communication between lesions. The findings were compared against survival data. More than one discrete contrast-enhancing lesion was present in 51 of the 151 patients (34%). Communication between lesions was identified in 47 of these, most commonly direct parenchymal spread (41 patients). The patients with multiple lesions had worse survival (median 176days, compared to 346days), but this difference was not statistically significant (p=0.253). These tumours more frequently involved deep structures (p<0.001) and the posterior fossa (p=0.045), both of which were associated with worse survival. The presence of multiple enhancing foci in glioblastoma is common, occurring in about one-third of patients, and the majority have multifocal disease. The FLAIR sequence is the crucial sequence for demonstrating a communication between lesions. The worse survival of these patients is, at least in large part related to more extensive tumour dissemination and more frequent involvement of key structures, rather than multiplicity per se.

  15. Human Gastric Cancer Kinase Profile and Prognostic Significance of MKK4 Kinase

    PubMed Central

    Wu, Chew-Wun; Li, Anna F.-Y.; Chi, Chin-Wen; Huang, Chen Lung; Shen, King-Han; Liu, Wing-Yiu; Lin, Wen-chang

    2000-01-01

    Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles. PMID:10854223

  16. Survival and prognostic factors comparing stage IB 1 versus stage IB 2 cervical cancer treated with primary radical hysterectomy.

    PubMed

    Srisomboon, Jatupol; Kietpeerakool, Chumnan; Suprasert, Prapaporn; Manopanya, Manatsawee; Siriaree, Sitthicha; Charoenkwan, Kittipat; Cheewakriangkrai, Chalong; Sae-Teng, Charuwan

    2011-01-01

    This study was undertaken to compare the survival rates of stage IB 1 versus stage IB 2 cervical cancer patients and to evaluate the prognostic factors after treatment primarily with radical hysterectomy and pelvic lymphadenectomy (RHPL). Patients with stage IB cervical cancer undergoing primary RHPL at Chiang Mai University Hospital between January 2002 and December 2009 were evaluated for survival and recurrence. Clinicopathological variables were analyzed to identify the prognostic factors affecting the survival of the patients. During the study period, RHPL was performed on 570 stage IB 1 and 110 stage IB 2 cervical cancer patients. With a median follow-up of 48 months, the 5-year disease-free survivals were 98.1% and 82.8% respectively (p<0.001). Multivariate analysis identified four significant prognostic factors affecting survival including sub-staging, non-squamous cell carcinoma histology, lymph node metastasis and the presence of lymph-vascular space invasion. In conclusion, with a primary radical hysterectomy, stage IB 1 cervical cancer patients have a significantly better survival rate than those with stage IB 2. Significant prognostic factors for stage IB cervical cancer include tumor histology, nodal status, and the presence of lymph-vascular space invasion.

  17. Clinicopathological and Prognostic Factors in 106 Prostate Cancer Patients Aged ≤55 Years: A Single-Center Study in China

    PubMed Central

    Xu, Yan; Yang, Xueling; Si, Tongguo; Yu, Haipeng; Zhang, Weihao; Li, Yong; Guo, Zhi

    2016-01-01

    Background Early-onset prostate cancer patients (aged ≤55 years) from Western countries have been well characterized in previous studies. However, the clinicopathological and prognostic characteristics of early-onset Chinese prostate cancer patients have not yet been assessed. This study aimed to examine the clinicopathological and prognostic factors of prostate cancer patients aged ≤55 years in a single Chinese center. Material/Methods One hundred six prostate cancer patients aged ≤55 years with complete clinicopathological data who were treated at our hospital between January 2000 and June 2014 were selected for this study. Survival rate was investigated by Kaplan-Meier analysis, and prognostic factors were examined by univariate and multivariate analysis. Results The median time from the onset of symptoms to diagnosis was 3.5 months (range, 2–55 months). The median time after endocrine therapy to development of androgen-independent prostate cancer was 10.5 months. A total of 54 patients died (50.9%), of whom 96.2% died from prostate cancer. The 1-, 3-, and 5-year overall survival rates were 88.7%, 66.2%, and 36.0%, respectively. Univariate and multivariate analysis showed that T staging, visceral metastasis, pathological pattern, and Gleason sum were independent prognostic factors in these patients. Conclusions Prostate cancer patients aged ≤55 years are often omitted or misdiagnosed in China. Furthermore, the pathology patterns in this age group were mostly complicated with a high degree of malignancy. Late staging, visceral metastasis, pathological pattern, and high Gleason score were independent prognostic factors in these patients. Comprehensive therapy combined with local therapy is an effective treatment strategy. PMID:27771734

  18. Are salivary amylase and pH – Prognostic indicators of cancers?

    PubMed Central

    Ramya, Atmakuri Shanmukha; Uppala, Divya; Majumdar, Sumit; Surekha, Ch.; Deepak, K.G.K.

    2015-01-01

    Background Saliva, “Mirror of body's health” has long been of particular interest as a substitute for blood for disease diagnosis and monitoring. The radiation effects on salivary glands are of particular interest in which salivary amylase is a good indicator of salivary glands function. Thus, estimation of these parameters represents a reasonable approach in evaluation of patient's risk for disease occurrence, intensity and prognosis. Aim of study To evaluate and compare the pH and amylase levels in saliva of cancer patients prior to treatment, patients during treatment. Materials and methods Saliva samples of 90 individuals were taken which were divided into 3 groups - 30 individuals without cancer, 30 cancer patients prior treatment and 30 cancer patients during treatment. Materials used were pH strips and pH meter, Salivary Amylase assay. Results Statistical analysis – ANOVA with post-hoc Tukey's test. 1) Significant decrease in salivary amylase levels – in cancer patients, during treatment when compared to others. 2) Significant decrease in salivary pH levels in newly diagnosed cancer patients prior to treatment. Conclusion To conclude, pH strips and pH meter showed to be a useful tool in the measurement of pH of saliva in individuals with and without cancer. This study showed that cancer patients without treatment have a lower pH of saliva. Treatment increased the pH of the saliva to a more alkaline level whereas amylase levels decreased in those subjects. Therefore those parameters can be an area of further research with an increased sample size, which in-turn may help in opening the doors for new dimension in non invasive prognostic markers. PMID:26258019

  19. Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer.

    PubMed

    Dai, Congqi; Geng, Ruixuan; Wang, Chenchen; Wong, Angela; Qing, Min; Hu, Jianjun; Sun, Yu; Lo, A W I; Li, Jin

    2016-12-01

    Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation. The data revealed that higher TIL density correlated with less risk of disease progression, and exhibited survival benefits in gastric cancer patients, and PD-L1 positivity showed a significant association with the presence of high TIL infiltration. Furthermore, real-time quantitative polymerase chain reaction was performed to detect expression of multiple immune checkpoints with the relation to clinical outcome in 139 samples randomly selected from the same cohort, and higher messenger RNA levels of most immune checkpoints were associated with favorable outcome, while consistently showing a positive correlation with interferon gamma levels. In situ hybridization was used to determine the localization of Epstein-Barr virus (EBV) in 97 specimens, and showed EBV-positive gastric cancer samples correlated with PD-L1 expression and increased TIL density. These results suggest that induction of immune checkpoint within gastric cancer patients reflects a high immune infiltration density, especially in those with EBV-associated gastric cancer, which may direct patient selection for checkpoint blockade therapy.

  20. Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients.

    PubMed

    Nagai, Maria Aparecida; Gerhard, Renê; Fregnani, José Humberto T G; Nonogaki, Suely; Rierger, Regina Barbosa; Netto, Mário Mourão; Soares, Fernando A

    2011-02-01

    An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful

  1. Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer

    PubMed Central

    Le Teuff, Gwénaël; Marguet, Sophie; Lantuejoul, Sylvie; Dunant, Ariane; Graziano, Stephen; Pirker, Robert; Douillard, Jean-Yves; Le Chevalier, Thierry; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Popper, Helmut; Soria, Jean-Charles; Shepherd, Frances A.; Seymour, Lesley; Tsao, Ming Sound

    2016-01-01

    Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer. PMID:26834066

  2. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  3. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  4. Prostate cancer stem/progenitor cells: identification, characterization, and implications.

    PubMed

    Tang, Dean G; Patrawala, Lubna; Calhoun, Tammy; Bhatia, Bobby; Choy, Grace; Schneider-Broussard, Robin; Jeter, Collene

    2007-01-01

    Several solid tumors have now been shown to contain stem cell-like cells called cancer stem cells (CSC). These cells, although generally rare, appear to be highly tumorigenic and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. In this Perspective, we first provide our insight on how a CSC should be defined. We then summarize our current knowledge of stem/progenitor cells in the normal human prostate (NHP), an organ highly susceptible to hyperproliferative diseases such as benign prostate hyperplasia (BPH) and prostate cancer (PCa). We further review the evidence that cultured PCa cells, xenograft prostate tumors, and patient tumors may contain stem/progenitor cells. Along with our discussion, we present several methodologies that can be potentially used to identify putative tumor-reinitiating CSC. Finally, we present a hypothetical model for the hierarchical organization of human PCa cells and discuss the implications of this model in helping understand prostate carcinogenesis and design novel diagnostic, prognostic, and therapeutic approaches.

  5. Prognostic Role of the Pretreatment C-Reactive Protein/Albumin Ratio in Solid Cancers: A Meta-Analysis

    PubMed Central

    Li, Nan; Tian, Guang-Wei; Wang, Ying; Zhang, Hui; Wang, Zi-hui; Li, Guang

    2017-01-01

    The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58–2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients. PMID:28128229

  6. Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis

    PubMed Central

    Yuan, Xiangliang; Xie, Guohua; Ma, Yanhui; Shen, Lisong

    2015-01-01

    Background The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer. Materials and Methods A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted. Results This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85). Conclusion Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer. PMID:26098665

  7. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer

    PubMed Central

    Peixoto, Renata D’Alpino; Speers, Caroline; McGahan, Colleen E; Renouf, Daniel J; Schaeffer, David F; Kennecke, Hagen F

    2015-01-01

    Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control. PMID:25891650

  8. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

    PubMed

    Peixoto, Renata D'Alpino; Speers, Caroline; McGahan, Colleen E; Renouf, Daniel J; Schaeffer, David F; Kennecke, Hagen F

    2015-08-01

    Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus ≤ 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

  9. Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis

    PubMed Central

    LIANG, Bin; LI, Yunhui

    2014-01-01

    Abstract Background Vascular endothelial growth factor (VEGF)-C, as a lymphangiogenic factor, plays important roles in the progression of several malignancies. However, its clinical prognostic value in breast cancer still remains controversial. We performed a meta-analysis of available studies to assess the association between VEGF-C expression and the ou-tcomes of breast cancer patients Methods We searched eligible studies in three English databases (MEDLINE, EMBASE, and Web of Science) and two Chinese databases (Wanfang and Chinese National Knowledge Infrastructure databases). Key words used in the research included ‘VEGF-C”, “breast cancer”, “immunohistochemistry”, “breast neoplasma(s)”, “breast carcinoma”, “metastasis”, and “prognosis”. Fourteen studies with a total of 1, 573 breast cancer cases were finally included into the meta-analysis. The pooled odds ratios (ORs) with the corresponding 95% confidence interval (95% CIs) for lymph node metastasis, overall survival, and disease-free survival were calculated by using fixed-effects or random-effects models. Heterogeneity and publication bias were also assessed. Results Meta-analysis of random-effects model showed VEGF-C expression was associated with lymph node metastasis in patients with breast cancer (random-effects, OR = 2.14; 95 % CI 1.21—3.77, P = 0.009). VEGF-C expression was associated with poorer overall survival (fixed-effects, OR = 2.46, 95% CI: 1.46—4.14, P < 0.001) and disease-free survival (fixed-effects, OR = 2.10, 95% CI: 1.32—3.35, P = 0.002) in patients with breast cancer. Conclusion VEGF-C expression is positively associated with lymph node metastasis in breast cancer, and VEGF-C detection in breast cancer might be an effective and feasible means to predict outcome. PMID:26060735

  10. Non-invasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer

    PubMed Central

    Mathé, Ewy A.; Patterson, Andrew D.; Haznadar, Majda; Manna, Soumen K.; Krausz, Kristopher W.; Bowman, Elise D.; Shields, Peter G.; Idle, Jeffrey R.; Smith, Philip B.; Anami, Katsuhiro; Kazandjian, Dickran G.; Hatzakis, Emmanuel; Gonzalez, Frank J.; Harris, Curtis C.

    2014-01-01

    Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non–small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I–II cases, important for early detection, and also associated with worse prognosis in stage I–II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 – 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. PMID:24736543

  11. The clinicopathological and prognostic features of Chinese and Japanese inpatients with lung cancer

    PubMed Central

    Li, Qing-chang; Liu, Jia-jie; Liu, Li-li; Yang, Xue-feng; Jiang, Hua-mao; Zheng, Hua-chuan

    2016-01-01

    Here, we retrospectively compared the differences in clinicopathological behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1, n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka, n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and large cell carcinomas than Chinese patients (p<0.05). Survival analysis showed that tumor size was employed as a prognostic factor for the Japanese and Chinese cancer patients (p<0.05). In DMU and CMUS, the ratios of female patients or adenocarcinoma were higher than other hospitals (p<0.05), while the patients from CMUT and CMU1 were younger than the others (p<0.05). The ratios of squamous cell carcinoma from CMUT, CMU1 and JMU were higher than the others, while it was the same for the ratio of large and small cell carcinoma in Takaoka and CMU1 (p<0.05). TNM staging was higher in CMUT than JMU and Takaoka (p<0.05). The female patients of lung cancer showed young prone, large tumor size, a high ratio of adenocarcinoma and advanced TNM staging in comparison to the counterpart (p<0.05). The younger patients of lung cancer displayed smaller tumor size, higher ratio of adenocarcinoma, lower TNM staging than the elder in Takaoka (p<0.05). There were more aggressive behaviors and shorter survival time for Chinese than Japanese lung cancer patients. The prevention of lung cancer should be strengthened by establishing a systematic and effective screening strategy, especially for the young and female patients. PMID:27608841

  12. Prognostic value of tumour cell detection in peripheral blood of breast cancer patients.

    PubMed

    Zach, O; Kasparu, H; Wagner, H; Krieger, O; Lutz, D

    2002-01-01

    To investigate the prognostic value of tumour cells in peripheral blood (pB) of breast cancer (BC) patients, pB samples from 143 patients with benign lesions of the breast and from 467 BC patients were tested via a nested RT-PCR assay for mammaglobin mRNA. No sample from patients with benign lesions of the breast was found to be mammaglobin positive in contrast to 5/310 (2%) BC patients with no evidence of disease (NED) and 46/157 (29%) patients with metastatic disease (MD). Two hundred and eighteen BC patients with NED were followed for at least 12 months. All five mammaglobin-positive BC patients relapsed 1-13 months after first examination of positive pB samples in contrast to 27/213 (13%) patients without detectable tumour cells in pB. Fifty-nine BC patients with MD were tested for mammaglobin expression in pB at the time of first diagnosis of MD; 20 of them (34%) were mammaglobin positive. Patients were followed for a median of 19 months (2-51 months). During this time, 19/59 (32%) died due to tumour progression. In Kaplan-Meier survival analysis, BC patients with mammaglobin-negative pB samples at time of diagnosis of MD lived significantly longer than mammaglobin-positive patients (log-rank test: P = 0.0013). In addition, mammaglobin was an independent prognostic parameter and the difference reached significance in univariate as well as in multivariate analysis (P < 0.01). We conclude that the presence of tumour cells in pB of BC patients is of prognostic value.

  13. The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

    SciTech Connect

    Rutkowski, Tomasz Suwinski, Rafal; Idasiak, Adam

    2007-11-15

    Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl). Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.

  14. Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer.

    PubMed

    Rachagani, Satyanarayana; Macha, Muzafar A; Heimann, Nicholas; Seshacharyulu, Parthasarathy; Haridas, Dhanya; Chugh, Seema; Batra, Surinder K

    2015-01-01

    Despite considerable progress being made in understanding pancreatic cancer (PC) pathogenesis, it still remains the 10th most often diagnosed malignancy in the world and 4th leading cause of cancer related deaths in the United States with a five year survival rate of only 6%. The aggressive nature, lack of early diagnostic and prognostic markers, late clinical presentation, and limited efficacy of existing treatment regimens make PC a lethal cancer with high mortality and poor prognosis. Therefore, novel reliable biomarkers and molecular targets are urgently needed to combat this deadly disease. MicroRNAs (miRNAs) are short (19-24 nucleotides) non-coding RNA molecules implicated in the regulation of gene expression at post-transcriptional level and play significant roles in various physiological and pathological conditions. Aberrant expression of miRNAs has been reported in several cancers including PC and is implicated in PC pathogenesis and progression, suggesting their utility in diagnosis, prognosis and therapy. In this review, we summarize the role of several miRNAs that regulate various oncogenes (KRAS) and tumor suppressor genes (p53, p16, SMAD4, etc.) involved in PC development, their prospective roles as diagnostic and prognostic markers and as a therapeutic targets.

  15. Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer

    PubMed Central

    Rachagani, Satyanarayana; Macha, Muzafar A.; Heimann, Nicholas; Seshacharyulu, Parthasarathy; Haridas, Dhanya; Chugh, Seema; Batra, Surinder K.

    2014-01-01

    Despite considerable progress being made in understanding pancreatic cancer (PC) pathogenesis, it still remains the 10th most often diagnosed malignancy in the world and 4th leading cause of cancer related deaths in the United States with a five year survival rate of only 6%. The aggressive nature, lack of early diagnostic and prognostic markers, late clinical presentation, and limited efficacy of existing treatment regimens makes PC a lethal cancer with high mortality and poor prognosis. Therefore, novel reliable biomarkers and molecular targets are urgently needed to combat this deadly disease. MicroRNAs (miRNAs) are short (19–24 nucleotides) non-coding RNA molecules implicated in the regulation of gene expression at post-transcriptional level and play significant roles in various physiological and pathological conditions. Aberrant expression of miRNAs has been reported in several cancers including PC and is implicated in PC pathogenesis and progression, suggesting their utility in diagnosis, prognosis and therapy. In this review, we summarize the role of several miRNAs that regulate various oncogenes (KRAS) and tumor suppressor genes (p53, p16, SMAD4 etc) involved in PC development, their prospective roles as diagnostic and prognostic markers and their therapeutic targets. PMID:25453266

  16. Clinicopathological features and prognostic factors of young breast cancers in Eastern Guangdong of China

    PubMed Central

    Wei, Jin-Tao; Huang, Wen-He; Du, Cai-Wen; Qiu, Si-Qi; Wei, Xiao-Long; Liu, Jing; Zhang, Guo-Jun

    2014-01-01

    Breast cancer in young women is typically with higher proportion of adverse pathological features. Breast cancer with BRCA1 mutation is often early-onset, and is usually associated with triple negative phenotpe. In this study, we aim to analyze the clinicopathological characteristics and prognosis in young breast cancer patients (≤35 years old) comparing to non-young patients (>35 years old). A total of 1913 cases of primary breast carcinoma with stage I–III were enrolled, with 283 cases diagnosed as young patients. No significant difference was observed in tumor size, TNM staging, lymph node metastasis, ER, HER-2 or histological grade between young and non-young patients. Multivariate analysis demonstrated that age was an independent prognostic factor for overall survival (OS). In 70 samples of young patients available, BRCA1 was immunohistochemically positive 85.7% in cytoplasm and 41.4% in nuclear. BRCA1 nuclear expression is not significantly associated with clinicopathological characteristics in young breast cancer patients. PMID:24942640

  17. Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer

    PubMed Central

    Prislei, Silvia; Martinelli, Enrica; Zannoni, Gian Franco; Petrillo, Marco; Filippetti, Flavia; Mariani, Marisa; Mozzetti, Simona; Raspaglio, Giuseppina; Scambia, Giovanni; Ferlini, Cristiano

    2015-01-01

    ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3′UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer. PMID:26136338

  18. The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

    PubMed

    Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

    2016-10-01

    HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.

  19. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    PubMed Central

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  20. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients.

    PubMed

    Zhang, Minghui; Zhang, Xiaosan; Zhao, Shu; Wang, Yan; Di, Wenyu; Zhao, Gangling; Yang, Maopeng; Zhang, Qingyuan

    2014-12-01

    Triple-negative breast cancer (TNBC) is a particular type of breast cancer which is characterized by its biological aggressiveness, worse prognosis, and lack of prognostic markers or therapeutic targets in contrast with hormonal receptor-positive and human epidermal growth factor receptor 2-positive (HER2+) breast cancers. We aimed to evaluate survivin and epidermal growth factor receptor (EGFR) expression and their prognostic value and determine their relationships with the clinicopathological parameters of TNBC. A total of 136 patients who had undergone a resection of primary TNBC were enrolled at the Third Affiliated Hospital of Harbin Medical University from March 2003 to September 2005. Expression of ER, PR, HER2, EGFR, and survivin was assessed by immunohistochemistry. The association of TNBC and other clinicopathological variables and the prognostic value of survivin and EGFR expression were evaluated. Survivin was expressed in 62 (45.6 %) cases and EGFR was expressed in 82 (60.3 %) cases. Survivin expression was associated with menopausal status (P = 0.011), tumor size (P = 0.037), and lymph node status (P = 0.001). EGFR expression was associated with menopausal status (P = 0.029), lymph node status (P = 0.004), P53 expression (P = 0.001), Ki-67 expression (P = 0.028), and lymphatic vascular invasion (P = 0.037). A multivariate analysis demonstrated that tumor size (hazard ratio (HR) 1.587, 95 % confidence interval (CI) 1.081–2.330, P = 0.018 for disease-free survival (DFS); HR 1.606, 95%CI 1.096–2.354, P = 0.015 for overall survival (OS)), lymph node status (HR 2.873, 95%CI 1.544–5.344, P = 0.001 for DFS; HR 2.915, 95%CI 1.553–5.471, P = 0.001 for OS), tumor grade (HR 1.914, 95%CI 1.218–3.007, P = 0.005 for DFS; HR 1.983, 95%CI 1.228–3.203, P = 0.005 for OS), EGFR (HR 3.008, 95%CI 1.331–6.792, P = 0.008 for DFS; HR 3.151, 95%CI 1.374–7.226, P = 0.007 for OS), and survivin (HR 1

  1. Prognostic and Safety Roles in Laparoscopic Versus Abdominal Radical Hysterectomy in Cervical Cancer: A Meta-analysis

    PubMed Central

    Cao, Tiefeng; Feng, Yanling; Huang, Qidan; Wan, Ting

    2015-01-01

    Abstract Objective: Studies comparing the prognostic results between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in cervical cancer reported contradictory results. We aimed to evaluate the prognostic and safety roles of LRH by pooling studies in a meta-analysis. Materials and Methods: Original articles were searched in PubMed, EMBASE, and the Cochrane Library. The survival results (5-year disease-free survival [DFS], 5-year overall survival [OS], and recurrence rate [RR]), safety parameters (intra-, peri-, and postoperative complication rates and postoperative bowel or bladder recovery days), efficiency parameters (pelvic/para-aortic lymph nodes removed), and other parameters (operative time, estimated blood loss, and hospital of stay) between the two approaches were reviewed. Results: For the 2922 cases identified, DFS, OS, and RR did not differ in balanced prognostic factors, including lymph node metastasis, Stage IIB or above, non–squamous cancer histology, grade G3, lymphovascular space invasion, tumor size ≥4 cm, and positive parametrial and vaginal margin rates. Meanwhile, LRH was associated with higher complication rates and a shorter time to the recovery of bowel or bladder function than for ARH. The number of removed pelvic or para-aortic lymph nodes did not significantly differ. Other parameters showed LRH was associated with a longer operative time, less blood loss, and a shorter length of hospital stay. The survival and prognostic results did not differ in balanced prognostic factors. Conclusions: LRH is safe and has lower operative complication rates than ARH. PMID:26584414

  2. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    PubMed Central

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan; Skovlund, Eva; Glimelius, Bengt; Pfeiffer, Per; Johansen, Julia S.; Kure, Elin H.; Ikdahl, Tone; Tveit, Kjell Magne; Christoffersen, Thoralf; Guren, Tormod Kyrre

    2016-01-01

    Objectives The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004). Materials and Methods IL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated. Conclusions High baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status. PMID:27738330

  3. Circulating Fibroblast Growth Factor 21 (Fgf21) as Diagnostic and Prognostic Biomarker in Renal Cancer

    PubMed Central

    Knott, ME; Minatta, JN; Roulet, L; Gueglio, G; Pasik, L; Ranuncolo, SM; Nuñez, M; Puricelli, L; De Lorenzo, MS

    2016-01-01

    Background The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. Materials and Methods Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank “Biobanco Público de Muestras Séricas Oncológicas” (BPMSO) of the “Instituto de Oncología “Ángel H. Roffo”. Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. Results One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. Conclusion Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival. PMID:27358750

  4. Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era-experience from a tertiary oncology centre in Southern India.

    PubMed

    Kuntegowdanahalli, Lakshmaiah Chinnagiriyappa; Kanakasetty, Govind Babu; Thanky, Aditi Harsh; Dasappa, Lokanatha; Jacob, Linu Abraham; Mallekavu, Suresh Babu; Lakkavalli, Rajeev Krishnappa; Kadabur, Lokesh N; Haleshappa, Rudresha Antapura

    2016-01-01

    Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.

  5. AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.

    PubMed

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G; Fasching, Peter A; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth; Rose, Michael; Dahl, Edgar

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.

  6. Prognostic Value of MammaPrint® in Invasive Lobular Breast Cancer

    PubMed Central

    Beumer, Inès J.; Persoon, Marion; Witteveen, Anke; Dreezen, Christa; Chin, Suet-Feung; Sammut, Stephen-John; Snel, Mireille; Caldas, Carlos; Linn, Sabine; van ’t Veer, Laura J.; Bernards, Rene; Glas, Annuska M.

    2016-01-01

    BACKGROUND MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup. STUDY AIM The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. MATERIALS AND METHODS Univariate and multivariate survival associations for overall survival (OS), distant metastasis-free interval (DMFI), and distant metastasis-free survival (DMFS) were studied in a study population of 217 early-stage ILC breast cancer patients from five different clinical studies. RESULTS AND DISCUSSION A significant association between MammaPrint High Risk and poor clinical outcome was shown for OS, DMFI, and DMFS. A subanalysis was performed on the lymph node-negative study population. In the lymph node-negative study population, we report an up to 11 times higher change in the diagnosis of an event in the MammaPrint High Risk group. For DMFI, the reported hazard ratio is 11.1 (95% confidence interval = 2.3–53.0). CONCLUSION Study results validate MammaPrint as an independent factor for breast cancer patients with early-stage invasive lobular breast cancer. Hazard ratios up to 11 in multivariate analyses emphasize the independent value of MammaPrint, specifically in lymph node-negative ILC breast cancers. PMID:27980389

  7. Tracheal cancer – treatment results, prognostic factors and incidence of other neoplasms

    PubMed Central

    Napieralska, Aleksandra; Miszczyk, Leszek

    2016-01-01

    Abstract Background Tracheal cancers (TC) are rare and treatment results that are reported are typically not satisfactory. The purpose of this research was assessment of the results of treatment of TC patients, identification of potential additional surgery candidates, evaluation of prognostic factors, and assessment of the occurrence of other malignancies. Patients and methods The Regional Cancer Database and the Hospital Database were searched for patients with tracheal neoplasms. Fifty-eight of 418 patients identified initially, met the inclusion criteria (primary TC with confirmed histology and complete treatment records). Standard statistical tests were used. Results Squamous cell carcinoma (SCC; 63.8%) and adenoid cystic carcinoma (ACC; 15.5%) were the most commonly diagnosed histological types of TC. Radiotherapy was delivered in 48 cases, surgery or endoscopic resection in 20, and chemotherapy in 14. TC was diagnosed as a second cancer in 10 patients, in 1 patient it occurred prior to the lung cancer, and in 1 was diagnosed simultaneously. During the median follow-up of 12.7 months, 85.5% of the patients died because of the disease. Local recurrence occurred in 17% cases. In univariate analysis, patients with ACC had statistically better five-year overall survival (77.8%) than those diagnosed with SCC (8.4%, p = 0.0001). Radiotherapy, performance status and haemoptysis were factors significantly influencing overall survival (OS) in the multivariate analysis. Among patients who were not treated surgically, 15–26% were found to constitute additional surgery candidates, depending on the selection criteria. Conclusions The diagnostic workup should be focused on the identification of TC patients suitable for invasive treatment and radiotherapy. Respiratory system cancer survivors can be considered a risk group for tracheal cancer. Radiotherapy constitutes an important part of the treatment of patients with TC. PMID:27904449

  8. Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer

    PubMed Central

    Wang, Peng; Ning, Shangwei; Zhang, Yunpeng; Li, Ronghong; Ye, Jingrun; Zhao, Zuxianglan; Zhi, Hui; Wang, Tingting; Guo, Zheng; Li, Xia

    2015-01-01

    Recent studies have suggested that long non-coding RNAs (lncRNAs) can interact with microRNAs (miRNAs) and indirectly regulate miRNA targets though competing interactions. However, the molecular mechanisms underlying these interactions are still largely unknown. In this study, these lncRNA–miRNA–gene interactions were defined as lncRNA-associated competing triplets (LncACTs), and an integrated pipeline was developed to identify lncACTs that are active in cancer. Competing lncRNAs had sponge features distinct from non-competing lncRNAs. In the lncACT cross-talk network, disease-associated lncRNAs, miRNAs and coding-genes showed specific topological patterns indicative of their competence and control of communication within the network. The construction of global competing activity profiles revealed that lncACTs had high activity specific to cancers. Analyses of clustered lncACTs revealed that they were enriched in various cancer-related biological processes. Based on the global cross-talk network and cluster analyses, nine cancer-specific sub-networks were constructed. H19- and BRCA1/2-associated lncACTs were able to discriminate between two groups of patients with different clinical outcomes. Disease-associated lncACTs also showed variable competing patterns across normal and cancer patient samples. In summary, this study uncovered and systematically characterized global properties of human lncACTs that may have prognostic value for predicting clinical outcome in cancer patients. PMID:25800746

  9. 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

  10. Prognostic and Therapeutic Implications of Statin and Aspirin Therapy in Individuals With Nonobstructive Coronary Artery Disease

    PubMed Central

    Chow, Benjamin J.W.; Small, Gary; Yam, Yeung; Chen, Li; McPherson, Ruth; Achenbach, Stephan; Al-Mallah, Mouaz; Berman, Daniel S.; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor Y.; Chinnaiyan, Kavitha; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gundrun; Hadamitzky, Martin; Hausleiter, Jörg; Karlsberg, Ronald P.; Kaufmann, Philipp A.; Kim, Yong-Jin; Leipsic, Jonathon; LaBounty, Troy; Lin, Fay; Maffei, Erica; Raff, Gilbert L.; Shaw, Leslee J.; Villines, Todd C.; Min, James K.

    2015-01-01

    Objective We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Approach and Results Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%–49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%–12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28–0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19–0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30–1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. Conclusions The presence and extent of nonobstructive

  11. Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer

    PubMed Central

    2012-01-01

    Background The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells. Methods On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity. Results The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality. Conclusions Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer. PMID:22353218

  12. Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study.

    PubMed

    Ben Néjima, Dalel; Ben Zarkouna, Yosr; Gammoudi, Amor; Manai, Mohamed; Boussen, Hamouda

    2015-05-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

  13. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  14. Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: a meta-analysis

    PubMed Central

    Cai, Aizhen; Wu, Xiaosong; Cui, Jianxin; Li, Jiyang; Qiao, Zhi; Wei, Bo; Chen, Lin

    2017-01-01

    Background Circulating tumor DNA (ctDNA) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). However, its diagnostic and prognostic value in gastric cancer still remains unclear. Results A total of 16 studies comprising 1193 GC patients met our inclusion criteria. The pooled sensitivity and specificity were 0.62 (95% confidence intervals (CI) 0.59−0.65) and 0.95 (95% CI 0.93–0.96), respectively. The AUSROC (area under SROC) curve was 0.94 (95% CI 0.89–0.98). The results showed that the presence of certain ctDNA markers was associated with larger tumor size (OR: 0.26, 95% CI 0.11–0.61, p = 0.002), TNM stage (I + II/III + IV, OR: 0.11, 95% CI 0.07−0.17, p = 0.000), as well as H. pylori infection. (H.p negative/H.p positive, OR: 0.57, 95% CI 0.36–0.91, p = 0.018). Moreover, there was also a significant association between the presence of ctDNA and worse overall survival (HR 1.77, 95% CI 1.38−2.28, p < 0.001), as well as disease-free survival (HR 4.36, 95% CI 3.08−6.16, p < 0.001). Materials and Methods Pubmed, Embase, Cochrane Library and Web of Science databases were searched for relating literature published up until November 30, 2016. Diagnostic accuracy variables were pooled by the Meta-Disc software. Engauge Digitizer and Stata software were applied for prognostic data extraction and analysis. Conclusions Our meta-analysis indicates the detection of certain ctDNA targets is significantly associated with poor prognosis of GC patients, with high specificity and relatively moderate sensitivity. PMID:28009985

  15. A Prognostic Index for Predicting Lymph Node Metastasis in Minor Salivary Gland Cancer

    SciTech Connect

    Lloyd, Shane; Yu, James B.; Ross, Douglas A.; Wilson, Lynn D.; Decker, Roy H.

    2010-01-15

    Purpose: Large studies examining the clinical and pathological factors associated with nodal metastasis in minor salivary gland cancer are lacking in the literature. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2,667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. Results: Four hundred twenty-six (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariate analysis included increasing age, male sex, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, including male sex, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. Conclusions: A prognostic index using the four clinicopathological factors listed here can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and should be validated in further clinical studies.

  16. Prognostic value of ERG, PTEN, CRISP3 and SPINK1 in predicting biochemical recurrence in prostate cancer

    PubMed Central

    NOH, BYEONG-JOO; SUNG, JI-YOUN; KIM, YOUN WHA; CHANG, SUNG-GOO; PARK, YONG-KOO

    2016-01-01

    The established prognostic factors associated with prostatic adenocarcinoma are the Gleason score, pathological T staging and serum prostatic-specific antigen (PSA) level. However, these prognostic factors alone are not sufficient for predicting prognostic characteristics, including early stage or advanced prostate cancer, presence of metastasis or disease-related mortality. The purpose of the present study was to simultaneously evaluate the prognostic value and associations of four biomarkers, namely, transcriptional regulator ERG (ERG), phosphatase and tensin homolog (PTEN), cysteine-rich secretory protein 3 (CRISP3) and serine protease inhibitor Kazal type I (SPINK1), and to conduct risk stratification of prostate cancer for use in patient management. A total of 68 formalin-fixed, paraffin-embedded, prostate cancer samples from radical prostatectomies were obtained in the Kyung Hee University Hospital (Seoul, Korea) and were studied immunohistochemically for ERG, PTEN, CRISP3 and SPINK1 to determine the proportion and intensity of staining. SPINK1 expression was mutually exclusive of ERG expression (P=0.001). The loss of PTEN and high CRISP3 expression are unfavorable indicators for prostate cancer, as PTEN loss was associated with shorter biochemical recurrence (BCR) (P=0.039), and high CRISP3 expression was associated with increased BCR (P<0.001) and cancer-related mortalities (P=0.011). Using the combination of low PTEN and high CRISP3 expression enables attention to be focused on patients who exhibit a poor prognosis. Subgrouping of patients, into high-risk and low-risk categories, was correlated with BCR-free survival in prostate cancer upon multivariate analysis (P=0.030). Overall, low PTEN and high CRISP3 expression significantly characterize the subgroups of prostate cancer that have a poor prognosis for BCR. PMID:27284364

  17. ADAMTS6 suppresses tumor progression via the ERK signaling pathway and serves as a prognostic marker in human breast cancer

    PubMed Central

    Xie, Keqi; Wang, Zhu; Wang, Yanping; Zheng, Hong

    2016-01-01

    A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics. The extracellular signal-regulated kinase (ERK) pathway was partially involved in ADAMTS6-mediated inhibition of BC development, and miR-221-3p was identified as a predicted target for ADAMTS6. Results from the luciferase assay confirmed that miR-221-3p directly inhibited ADAMTS6 expression by binding its 3′-untranslated region. In addition, immunohistochemistry data from specimens from 182 BC patients showed that high ADAMTS6 expression was significantly correlated with favorable disease-free survival (DFS, p = 0.045). Subgroup analysis of patients with ER positive, PR positive or HER-2 negative tumors revealed that high ADAMTS6 expression more strongly extended DFS compared to low expression (p = 0.004, p = 0.009, p = 0.017). Multivariate analyses confirmed that ADAMTS6 expression was an independent risk factor for DFS (p = 0.011). Together, these data demonstrate that ADAMTS6 inhibits tumor development by regulating the ERK pathway via binding of miR-221-3p. Thus, its expression may be a potential prognostic biomarker for BC. PMID:27542224

  18. Prognostic significance of new onset ascites in patients with pancreatic cancer

    PubMed Central

    Zervos, Emmanuel E; Osborne, Dana; Boe, Brian A; Luzardo, German; Goldin, Steven B; Rosemurgy, Alexander S

    2006-01-01

    Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III) underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm). All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm) presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention. PMID:16569225

  19. The Diagnostic and Prognostic Role of microRNA in Colorectal Cancer - a Comprehensive review.

    PubMed

    Mazeh, Haggi; Mizrahi, Ido; Ilyayev, Nadia; Halle, David; Brücher, Bjoern; Bilchik, Anton; Protic, Mladjan; Daumer, Martin; Stojadinovic, Alexander; Itzhak, Avital; Nissan, Aviram

    2013-01-01

    The discovery of microRNA, a group of regulatory short RNA fragments, has added a new dimension to the diagnosis and management of neoplastic diseases. Differential expression of microRNA in a unique pattern in a wide range of tumor types enables researches to develop a microRNA-based assay for source identification of metastatic disease of unknown origin. This is just one example of many microRNA-based cancer diagnostic and prognostic assays in various phases of clinical research.Since colorectal cancer (CRC) is a phenotypic expression of multiple molecular pathways including chromosomal instability (CIN), micro-satellite instability (MIS) and CpG islands promoter hypermethylation (CIMP), there is no one-unique pattern of microRNA expression expected in this disease and indeed, there are multiple reports published, describing different patterns of microRNA expression in CRC.The scope of this manuscript is to provide a comprehensive review of the scientific literature describing the dysregulation of and the potential role for microRNA in the management of CRC. A Pubmed search was conducted using the following MeSH terms, "microRNA" and "colorectal cancer". Of the 493 publications screened, there were 57 papers describing dysregulation of microRNA in CRC.

  20. Significant prognostic value of circulating tumor cells in esophageal cancer patients: A meta-analysis.

    PubMed

    Wang, Shuyu; Du, Hongyang; Li, Guixia

    2017-02-02

    Esophageal cancer is the sixth leading cause of cancer death worldwide. Detection of circulating tumor cells (CTCs) is emerging as a novel strategy for predicting cancer patient prognosis. Here we performed a comprehensive literature search to identify relevant articles in EMbase, PubMed, EBSCO, OVID, Cochrane Database, CNKI, WanFangdata and VIPdata. Meta-analysis was conducted using Stata12.0 software, according to the inclusion and exclusion criteria, extracted data and assessment methodology. Thirteen eligible literature studies were included with a total of 979 esophageal squamous cell carcinoma patients, including 424 CTC-positive and 684 CTC-negative cases. Meta-analysis showed that the presence of CTCs was associated with both worse progression-free/disease-free survival [hazard ration (HR) = 2.32, 95% confidence interval (CI) = 1.57 - 3.43, p < 0.001] and poorer overall survival [HR = 2.64, 95% CI = 1.69 - 4.14, p < 0.001]. Further subgroup analyses demonstrated that CTC-positive patients also showed worse progression-free/disease-free survival and poorer overall survival in different subsets. In summary, our meta-analysis provides strong evidence that detection of CTCs in the peripheral blood is an independent prognostic indicator of poor outcome for esophageal squamous cell carcinoma patients.

  1. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    PubMed Central

    Kong, Pengfei; Wu, Ruiyan; Yang, Chenlu; Geng, Qirong; Liu, Jianjun; Chen, Shangxiang; Liu, Xuechao; Ye, Minting; He, Wenzhuo; Yang, Qiong; Xia, Liangping; Xu, Dazhi

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion. PMID:27381549

  2. Recursive Partitioning Analysis of Prognostic Factors for Survival in Patients With Advanced Cancer

    SciTech Connect

    Chow, Edward Abdolell, Mohamed; Panzarella, Tony; Harris, Kristin; Bezjak, Andrea; Warde, Padraig; Tannock, Ian

    2009-03-15

    Purpose: To construct a predictive model for survival of patients referred to the Rapid Response Radiotherapy Program using recursive partitioning (RP). Methods and Materials: We analyzed 16 factors characterizing patients with metastases at first referral to the Rapid Response Radiotherapy Program for palliative radiotherapy in 1999 for their effect on survival. They included age, primary cancer site, site of metastases, weight loss ({>=}10% during the past 6 months), Karnofsky performance status (KPS), interval from the first diagnosis of cancer to the first consultation at the Rapid Response Radiotherapy Program, analgesic consumption within the previous 24 h, and the nine symptom scores from the Edmonton Symptom Assessment Scale. We used RP to develop a predictive model of survival for patients referred in 1999, followed by temporal validation using patients referred in 2000, and external validation using patients referred in 2002 to another institution. Results: The model was able to separate patients into three groups with different durations of survival that were defined by (1) KPS >60; (2) KPS {<=}60 with bone metastases only; and (3) KPS {<=}60 with other metastases. The model performed moderately well when applied to the validation sets, but a major limitation was that it led to an unequal distribution of patients, with a small proportion of patients in the intermediate group. Conclusion: We have demonstrated that RP can be used to predict the survival of patients with advanced cancer. However, this model has no advantages compared with our published prognostic models that use the survival prediction scores and number of risk factors.

  3. Prognostic value of Muc5AC in gastric cancer: A meta-analysis

    PubMed Central

    Zhang, Chuan-Tao; He, Ke-Cheng; Pan, Fei; Li, Yuan; Wu, Jiang

    2015-01-01

    AIM: To assess the correlation between decreased Muc5AC expression and patients’ survival and clinicopathological characteristics by conducting a meta-analysis. METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer. PMID:26420972

  4. Long-term prognostic impact of circulating tumour cells in gastric cancer patients

    PubMed Central

    Ito, Hiroaki; Sato, Jun; Tsujino, Yukio; Yamaguchi, Noriko; Kimura, Satoshi; Gohda, Keigo; Murakami, Katsuhiro; Onimaru, Manabu; Ohmori, Tohru; Ishikawa, Fumihiro; Inoue, Haruhiro

    2016-01-01

    AIM To analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034). CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer. PMID:28028372

  5. Role of perineural invasion as a prognostic factor in laryngeal cancer

    PubMed Central

    MESOLELLA, MASSIMO; IORIO, BRIGIDA; MISSO, GABRIELLA; LUCE, AMALIA; CIMMINO, MARIANO; IENGO, MAURIZIO; LANDI, MARIO; SPERLONGANO, PASQUALE; CARAGLIA, MICHELE; RICCIARDIELLO, FILIPPO

    2016-01-01

    The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT. PMID:27073523

  6. An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

    PubMed Central

    2010-01-01

    Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321

  7. Prognostic value of ERCC1 mRNA expression in non-small cell lung cancer, breast cancer, and gastric cancer in patients from Southern China

    PubMed Central

    Deng, Qiuhua; Yang, Haihong; Lin, Yongping; Qiu, Yuan; Gu, Xia; He, Ping; Zhao, Meiling; Wang, Hui; Xu, Yunjian; Lin, Yunen; Jiang, Juhong; He, Jianxing; Zhou, Jeff X

    2014-01-01

    Abstract: Background: Excision repair cross complementation group 1 (ERCC1) is a nucleotide excision repair pathway gene which provides protection against platinum-based chemotherapy-induced DNA damage. Methods: ERCC1 mRNA expression was quantified by quantitative real-time reverse-transcription PCR in paraffin-embedded non-small cell lung cancer (NSCLC; n = 357), gastric cancer (n = 106), and breast cancer (n = 363) tissues. Survival curves were generated by Kaplan-Meier analysis; Cox proportional multivariate regression analysis was applied. Results: ERCC1 mRNA expression was significantly higher in breast cancer than gastric cancer or NSCLC (both P < 0.0001), but not significantly different in NSCLC and gastric cancer (P = 0.119). In NSCLC, the low ERCC1 group had significantly longer disease free survival (DFS) than the high ERCC1 group (29.1 vs. 21.0 months, P < 0.0001); in the surgery alone and postoperative platinum-containing chemotherapy subgroups, DFS was significantly longer for the low ERCC1 groups than high ERCC1 groups (30.2 vs. 25.1 months, P = 0.018; 27.0 vs. 19.4 months, P < 0.0001, respectively). In gastric cancer patients receiving surgery alone, the low ERCC1 group had significantly longer overall survival than the high ERCC1 group (47.54 vs. 27.47 months, P = 0.018). Conclusions: High ERCC1 mRNA expression of the NSCLC tumor tissues was associated with poor disease-free survival (DFS), in both the surgery alone and postoperative platinum-containing chemotherapy subgroups. Meanwhile, low ERCC1 mRNA expression had significantly longer overall survival in gastric cancer patients receiving surgery alone. Therefore, ERCC1 expression was a prognostic factor and predictive marker in NSCLC, and gastric cancer after surgery alone, but was not a prognostic factor in breast cancer. PMID:25674197

  8. A 'new normal': Exploring the disruption of a poor prognostic cancer diagnosis using interviews and participant-produced photographs.

    PubMed

    Balmer, Claire; Griffiths, Frances; Dunn, Janet

    2015-09-01

    Cancer survival is increasing, and many people are living years after cancer treatment. For example, it is predicted that 46 per cent of men and 56 per cent of women diagnosed in 2007 in England and Wales will survive their cancer for 5 years or more. However, 'survivors' may be living with significant physical, psychological and social disruption caused by their illness. Furthermore, huge disparities exist in the outcomes for different cancer 'types', and there has been little investigation of those living with 'poor prognostic' cancers. Our aim was to explore the experience of living after the diagnosis of a poor prognostic cancer. Data were gathered from 30 people via interviews and participants' own photographs. Our findings suggest that a full 'recovery' may be impossible after a cancer diagnosis. Such diagnoses will continue to threaten biographical trajectory and self-identity forever. 'Returning to normal' was considered highly important for participants, but a changed normality had to be accepted in which lives were managed carefully and a constant fear of recurrence created liminality and made 'survivorship' ambiguous. Experience was often complicated by the social response associated with cancer that hindered communication and increased isolation. Participant-produced photographs, used here for the first time specifically by a sample of people with poor prognosis cancer, proved to be an acceptable data collection method and have added a poignancy and 'completeness' to the data that have arguably led to a more comprehensive understanding.

  9. Prognostic Value of Survivin in Locally Advanced Prostate Cancer: Study Based on RTOG 8610

    SciTech Connect

    Zhang Min; Ho, Alex; Hammond, Elizabeth H.; Suzuki, Yoshiyuki; Bermudez, R. Scott; Lee, R. Jeffrey; Pilepich, Michael; Shipley, William U.; Sandler, Howard; Khor, Li-Yan; Pollack, Alan; Chakravarti, Arnab

    2009-03-15

    Purpose: To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610. Methods and Materials: RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin. Results: Compared with patients with nuclear survivin intensity scores of {<=}191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25-0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16-0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density {<=}82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03-6.01; p = 0.0421). Conclusion: Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments.

  10. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

    PubMed

    Pompas-Veganzones, N; Sandonis, V; Perez-Lanzac, Alberto; Beltran, M; Beardo, P; Juárez, A; Vazquez, F; Cozar, J M; Alvarez-Ossorio, J L; Sanchez-Carbayo, Marta

    2016-10-01

    Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed

  11. Utility of Red Cell Distribution Width as a Prognostic Factor in Young Breast Cancer Patients

    PubMed Central

    Huang, Du-Ping; Ma, Rui-Min; Xiang, You-Qun

    2016-01-01

    Abstract The prognosis of breast cancer occurs in young women is usually poor. Red cell distribution width (RDW), 1 of many routinely examined parameters, has recently been proposed as a prognostic marker in solid tumors. The aim of our study was to assess the predictive value of RDW for survival in young women with breast cancer. We reviewed 203 consecutive young female patients (under 40) with invasive breast cancer diagnosed at the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2012. Preoperational RDW, clinicopathological information, and prognostic data were collected. RDW levels were divided into 2 groups: 161 patients with low RDW (≤13.75%) and 42 patients with high RDW (>13.75%). Clinicopathological differences between the 2 groups were calculated by chi-squared test and Wilcoxon rank-sum test. Kaplan–Meier survival analysis and Cox proportional hazard regression analyses were used to examine the effect of RDW on survival. We found that high RDW was significantly associated with larger tumor size (P = 0.002), positive lymph node metastases (P = 0.011), and advanced stages (P = 0.004). Patients with high RDW showed significantly lower disease-free survival (DFS; P < 0.001) and lower overall survival (OS) rate (P < 0.001) than patients with low RDW. Moreover, the Cox regression multivariate analysis revealed that high pretreatment DRW was independently correlated with poor DFS and OS, with hazard ratio 4.819 (95% confidence interval [CI] 2.291–10.138, P < 0.001) and 5.887 (95% CI 1.666–20.802, P = 0.006), respectively. In conclusion, our study demonstrated that pretreatment RDW may be associated with DFS and OS in young women with breast cancer. Further validation and feasibility studies are required before the result of our study can be considered for clinical practice. PMID:27124030

  12. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  13. Prostate Cancer Prognostic Factors Among Asian Patients Born in the US Compared to Those Born Abroad.

    PubMed

    Xu, Junjun; Goodman, Michael; Jemal, Ahemdin; Fedewa, Stacey A

    2015-06-01

    US surveillance data indicate that incidence of prostate cancer differs by place of birth among Asian men. However, it is less clear if the prognostic factors for prostate cancer also differ by place of birth. The study included 7,824 Asian prostate cancer patients diagnosed between 2004 and 2009 and reported to the Surveillance Epidemiology and End Results (SEER) program. Logistic regression models were used to evaluate the relation of place of birth (foreign born vs. US born) to three outcomes: prostate specific antigen (PSA) level, Gleason score, and T classification, adjusting for age, marital status, Rural-Urban Continuum Code, and SEER registry. All outcome variables were binary using different cutoffs: ≥ 4, ≥ 10 and ≥ 20 ng/ml for PSA; ≥ 7 and ≥ 8 for Gleason score; and ≥ T2 and ≥ T3 for T classification. Elevated PSA was more common among foreign born Asian men regardless of the cut point used. In the analysis comparing foreign born versus US born patients by ethnic group, the association with PSA was most pronounced at cut point of ≥ 20 ng/ml for Chinese men (OR 1.68, 95% CI 1.02-2.75), and at cut point of ≥ 4 ng/ml for Japanese men (OR 2.73, 95% CI 1.20-6.21). A statistically significant association with Gleason score was only found for Japanese men and only for the cutoff ≥ 7 (OR 1.71, 95% CI 1.12-2.61). There was no difference in clinical T classification between foreign-born and US-born Asian men. Inclusion of cases with missing place of birth or restriction of data to those who underwent radical prostatectomy did not substantially change the results. The data suggest that foreign-born Asian prostate cancer patients may have moderately elevated PSA levels at diagnosis compared with their US born counterparts. For the other prognostic markers, the associations were less consistent and did not form a discernible pattern.

  14. BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

    PubMed Central

    Lee, Y-K; Choi, E; Kim, M A; Park, P-G; Park, N-H; Lee, H

    2009-01-01

    Background: Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A. Methods: We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment. Results: The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (P<0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed. Conclusion: BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. PMID:19603021

  15. Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer

    PubMed Central

    Esfahani, Ali; Makhdami, Nima; Faramarzi, Elnaz; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Ghoreishi, Zohreh

    2016-01-01

    Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR) and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS). Then a score was defined as prealbumin/CRP based prognostic score (PCPS) to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n = 43) and those with nonmetastatic (n = 28) gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA) and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P = 0.005). Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted. PMID:26904109

  16. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    PubMed Central

    Demichelis, Sandra O; Isla-Larrain, Marina T; Cermignani, Luciano; Alberdi, Cecilio G; Segal-Eiras, Amada; Croce, María Virginia

    2011-01-01

    Objective In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis. Results All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased. Conclusion Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer. PMID:24367185

  17. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    SciTech Connect

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-12-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  18. The endocannabinoid system and cancer: therapeutic implication

    PubMed Central

    Guindon, Josée; Hohmann, Andrea G

    2011-01-01

    The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others). The main active ingredient of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), produces its effects through activation of CB1 and CB2 receptors. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are concentrated predominantly, although not exclusively, in cells of the immune system. Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid system and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer. This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed. Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients. Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21410463

  19. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    PubMed Central

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator

  20. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

    PubMed Central

    Dawson, S-J; Makretsov, N; Blows, F M; Driver, K E; Provenzano, E; Le Quesne, J; Baglietto, L; Severi, G; Giles, G G; McLean, C A; Callagy, G; Green, A R; Ellis, I; Gelmon, K; Turashvili, G; Leung, S; Aparicio, S; Huntsman, D; Caldas, C; Pharoah, P

    2010-01-01

    Background: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. Methods: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. Results: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). Conclusions: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work

  1. An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent

    PubMed Central

    Rajab, Ramzi; Fisher, Gabrielle; Kattan, Michael W; Foster, Christopher S; Møller, Henrik; Oliver, Tim; Reuter, Victor; Scardino, Peter T; Cuzick, Jack; Berney, Daniel M

    2013-01-01

    Treatment decisions on prostate cancer diagnosed by trans-urethral resection (TURP) of the prostate are difficult. The current TNM staging system for pT1 prostate cancer has not been re-evaluated for 25 years. Our objective was to optimise the predictive power of tumor extent measurements in TURP of the prostate specimens. A total of 914 patients diagnosed by TURP of the prostate between 1990 and 1996, managed conservatively were identified. The clinical end point was death from prostate cancer. Diagnostic serum prostate-specific antigen (PSA) and contemporary Gleason grading was available. Cancer extent was measured by the percentage of chips infiltrated by cancer. Death rates were compared by univariate and multivariate proportional hazards models, including baseline PSA and Gleason score. The percentage of positive chips was highly predictive of prostate cancer death when assessed as a continuous variable or as a grouped variable on the basis of and including the quintiles, quartiles, tertiles and median groups. In the univariate model, the most informative variable was a four group-split (≤ 10%, >10–25%, > 25–75% and > 75%); (HR = 2.08, 95% CI = 1.8–2.4, P < 0.0001). The same was true in a multivariate model (ΔX2 (1 d.f.) = 15.0, P = 0.0001). The current cutoff used by TNM (< = 5%) was sub-optimal (ΔX2 (1 d.f.) = 4.8, P = 0.023). The current TNM staging results in substantial loss of information. Staging by a four-group subdivision would substantially improve prognostication in patients with early stage disease and also may help to refine management decisions in patients who would do well with conservative treatments. PMID:20834240

  2. Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling

    PubMed Central

    Kristensen, Helle; Thomsen, Anni R.; Haldrup, Christa; Dyrskjøt, Lars; Høyer, Søren; Borre, Michael; Mouritzen, Peter; Ørntoft, Torben F.; Sørensen, Karina Dalsgaard

    2016-01-01

    Purpose This study investigates the diagnostic and prognostic biomarker potential of miRNAs in prostate cancer (PC). Results We identified several new deregulated miRNAs between non-malignant (NM) and PC tissue samples and between more/less aggressive PC subgroups. We also developed and validated a novel 13-miRNA diagnostic classifier with high sensitivity and specificity for PC. Finally, we trained a new 3-miRNA prognostic classifier (miR-185-5p+miR-221-3p+miR-326) that predicted time to biochemical recurrence (BCR) independently of routine clinicopathological variables in a training radical prostatectomy (RP) cohort (n = 126) as well as in two independent validation cohorts (n = 110 and n = 99). Experimental Design After RT-qPCR-based profiling of 752 miRNAs in 13 NM and 134 PC tissue samples (cohort 1), we selected 93 top candidate diagnostic/prognostic miRNAs for validation in two independent patient sets (cohort 2: 19 NM and 138 PC; cohort 3: 28 NM and 113 PC samples). Diagnostic potential was assessed by ROC curve analysis and prognostic potential by Kaplan-Meier, uni- and multivariate Cox regression analyses. BCR after RP was used as endpoint. Conclusions This is the first report of a miRNA signature with significant independent prognostic value demonstrated in three PC patient cohorts. PMID:27120795

  3. Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

    PubMed Central

    Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

    2013-01-01

    Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

  4. Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

    SciTech Connect

    Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W.; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J.

    2013-04-01

    Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.

  5. Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer

    PubMed Central

    Lu, Li; Wu, Menglin; Sun, Longhao; Li, Weidong; Fu, Weihua; Zhang, Xuening; Liu, Tong

    2016-01-01

    Abstract Background: In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers’ roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers’ clinicopathological features and association with prognosis in patients with gastric cancer. Methods: Eligible studies were identified and odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Heterogeneity and sensitivity were analyzed as well. Publication bias was assessed using funnel plots and Egger tests. Results: The meta-analysis included 26 studies involving 4729 patients. High expression of CD44 was associated with Lauren type (intestinal type) (OR, 1.53 [95% CI, 1.02–2.30]; P = 0.038) and lymphatic vessel invasion (OR, 1.36 [95% CI, 1.06–1.76]; P = 0.021). CD133 overexpression was related to high TNM stage (III/IV) (OR, 3.18 [95% CI, 2.48–4.07]; P = 0.000), high depth of invasion (T3/T4) (OR, 2.97 [95% CI, 2.20–4.03]; P = 0.000), lymph node metastasis (OR, 2.82 [95% CI, 2.16–3.69]; P = 0.000), vascular invasion (OR, 6.71 [95% CI, 1.63–27.63]; P = 0.008), and distant metastasis (OR, 2.32 [95% CI, 1.64–3.29]; P = 0.000). In addition, survival analysis demonstrated a significant association between CD44, as well as CD133 and poor 5-year overall survival (HR, 1.87 [95% CI, 1.55–2.26]; P = 0.000; HR, 2.07 [95% CI, 1.76–2.44]; P = 0.000, respectively). Conclusion: These data suggest that upregulated expression of CD44 and CD133 correlates with several clinicopathological features and poor prognosis. Since the related features do not overlap, combined detection of CD44 and CD133 expression can be an especially effective tool for pathological diagnosis

  6. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

    PubMed Central

    da Silva Oliveira, Kelly Cristina; Thomaz Araújo, Taíssa Maíra; Albuquerque, Camila Inagaki; Barata, Gabriela Alcantara; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Rodrigues Mello Junior, Fernando Augusto; Khayat, André Salim; de Assumpção, Paulo Pimentel; Rodriguez Burbano, Rommel Mário; Smith, Marília Cardoso; Calcagno, Danielle Queiroz

    2016-01-01

    Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity. PMID:27672290

  7. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer.

    PubMed

    da Silva Oliveira, Kelly Cristina; Thomaz Araújo, Taíssa Maíra; Albuquerque, Camila Inagaki; Barata, Gabriela Alcantara; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Rodrigues Mello Junior, Fernando Augusto; Khayat, André Salim; de Assumpção, Paulo Pimentel; Rodriguez Burbano, Rommel Mário; Smith, Marília Cardoso; Calcagno, Danielle Queiroz

    2016-09-21

    Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.

  8. Scoring of Prognostic Parameters in Patients with Unresectable Advanced or Recurrent Colorectal Cancer Undergoing Chemotherapy

    PubMed Central

    Ikeguchi, Masahide; Shimoda, Ryugo; Yamamoto, Manabu; Maeta, Yoshihiko; Ashida, Keigo; Saito, Hiroaki

    2013-01-01

    Background Suitable chemotherapy is needed to prolong the survival of patients with unresectable advanced or recurrent colorectal cancer. We scored the periodical changes of several prognostic markers during chemotherapy in patients with this type of cancer to discern the effectiveness of chemotherapy. Methods Twenty consecutive patients with unresectable advanced or recurrent colorectal cancer were enrolled. All patients underwent combination chemotherapy with oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin. Neutrophil/lymphocyte ratio (NLR), serum C-reactive protein (CRP), serum carcinoembryonic antigen (CEA) and serum albumin (ALB) were compared between the two periods (before chemotherapy and 3 months after it was started) in each patient. The scoring system was as follows: points are added when a patient shows a decrease of NLR, CRP and CEA and an increase of ALB at 3 months after the start of chemotherapy with a possible final score of +4. On the other hand, points are reduced if a patient shows an elevation of NLR, CRP and CEA and a decrease of ALB at 3 months after the start of chemotherapy with a possible final score of −4. Results At 3 months after the start of first line chemotherapy, 13 patients showed positive scores but 7 patients showed zero or minus scores. According to our scoring system, we found the mean survival time (MST) of the 13 patients with plus scores was 34 months and this was significantly better than that of the 7 patients who showed zero or minus scores (P = 0.0008). Conclusion Our new scoring system is useful but when we find that first line chemotherapy is ineffective, we need to change it to second line chemotherapy as soon as possible. That may be the best treatment for patients with unresectable advanced or recurrent colorectal cancer. PMID:24179314

  9. The Role of Steroid Sulfatase as a Prognostic Factor in Patients with Endometrial Cancer

    PubMed Central

    Lee, Won Moo; Jang, Ki-Seok; Koh, A Ra

    2016-01-01

    Purpose The aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis. Materials and Methods We conducted a retrospective study in 59 patients who underwent surgery with histologically confirmed endometrial cancer from January 2000 to December 2011 at Hanyang University Hospital. Immuno-histochemical staining of STS was performed using rabbit polyclonal anti-STS antibody. Results Sixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83±8.67 [95% confidence interval (CI): 112.84–146.82] months in the STS positive group (group A) and 111.06±7.17 (95% CI: 97.01–125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01±9.38 (95% CI: 110.63–147.38) months and 111.16±7.10 (95% CI: 97.24–125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis. Conclusion STS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research. PMID:26996578

  10. Prognostic value of microRNA-9 in cancers: a systematic review and meta-analysis

    PubMed Central

    Huang, Jin; Sun, Siwei; Liu, Yijie; Zhou, Pinghui; Yang, Huilin

    2016-01-01

    Recent studies revealed that different microRNA-9 (miR-9) expressions were associated with prognoses of different cancers. We conducted this meta-analysis to evaluate the prognostic value of miR-9. PubMed, Embase, Web of Science, and Cochrane Library (last update by November 30, 2015) were searched for literatures. A total of 17 studies from 16 articles were finally qualified and enrolled in this meta-analysis. Pooled analyses showed that a higher expression of miR-9 might predict poor overall survival (HR: 2.17, 95% CI: 1.39 – 3.41, P < 0.001 (7.23 * 10−4)), disease-free survival (HR: 5.22, 95% CI: 2.17 – 12.53, P < 0.001 (2.21 * 10−4)), and recurrence-free survival (HR: 1.57, 95% CI: 1.32 – 1.85, P < 0.001 (1.80*10−7)) in various carcinomas. However, results of subgroup analyses revealed that down-regulated miR-9 was associated with poor overall survival (HR: 0.45, 95% CI: 0.28 – 0.73, P < 0.001 (1.13*10−3)) and progress-free survival (HR: 0.46, 95% CI: 0.34 – 0.62, P < 0.001 (5.03*10−7)) in ovarian cancer patients. By subgroup analyses we also found that sample collecting time and patients’ origin had little influence on the result of OS. These results indicate that in most cancer types the highly expressed miR-9 is associated with poor survival of patients, whereas the down-regulated miR-9 may predict poor prognosis in patients with ovarian cancer. PMID:27563807

  11. Predictive and prognostic values of cancer-associated serum antigen (CASA) and cancer antigen 125 (CA 125) levels prior to second-look laparotomy for ovarian cancer.

    PubMed

    Kierkegaard, O; Mogensen, O; Mogensen, B; Jakobsen, A

    1995-11-01

    CA 125 and cancer-associated serum antigen (CASA) were measured prior to second-look laparotomy (SLL) to investigate their predictive and prognostic values in 93 patients treated for epithelial ovarian cancer FIGO stage II, III, or IV. Residual tumor was diagnosed at the SLL in 58 patients (62%). The optimal cutoff level was 15 U/ml for CA 125 and 8 U/ml for CASA. Using these levels, the sensitivity for detection of residual tumor was 40% for CA 125 and 22% for CASA. The combined use of the markers resulted in a sensitivity of 47% (diagnostic gain 6.9%; 95% confidence interval (CI), 0.14-13.44%). Microscopic tumor volumes were equally diagnosed by CASA and CA 125. The independent prognostic value of CA 125 (RR = 2.6; 95% CI, 2.0-3.2) and CASA (RR = 2.2; CI, 1.5-2.9) was established by means of Cox regression analysis of the covariation between survival, age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor at the primary operation and CA 125 and CASA before the SLL. In conclusion, we found that CASA could supplement CA 125 measurement prior to SLL and reduce the number of SLLs. Furthermore, CASA had an independent prognostic value for survival which may be used together with other information in the planning of further treatment of the individual patient.

  12. Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer

    PubMed Central

    Zhang, Tao; Tan, Xiang-Long; Xu, Yong; Wang, Zi-Zheng; Xiao, Chao-Hui; Liu, Rong

    2017-01-01

    Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. Methods: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted. Results: PANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-γ. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (χ2 = 4.550, P = 0.030), poor histological differentiation (χ2 = 5.690, P = 0.017), and lymph node metastasis (χ2 = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma. Conclusions: The study confirmed that high IDO expression in

  13. Multigene classifiers, prognostic factors, and predictors of breast cancer clinical outcome.

    PubMed

    Ross, Jeffrey S

    2009-07-01

    A series of multigene classifiers, prognostic and predictive tests have recently been introduced as potentially useful adjuncts for the management of recently diagnosed breast cancer patients. These tests have used both slide-based methods including immunohistochemistry and fluorescence in situ hybridization and nonmorphology driven molecular platforms including quantitative multiplex real time polymerase chain reaction and genomic microarray profiling. In this review, a series of partially and completely commercialized multigene assays are compared with the standard breast cancer clinico-pathologic variables and biomarkers and evaluated as to the level of their scientific validation, current clinical utility, regulatory approval status, and estimated cost-benefit. A comparison of the Oncotype Dx and MammaPrint assays indicates that the Oncotype Dx test has the advantages of an earlier commercial launch in the US, wide acceptance for payment by third party payors, the ease of use of formalin fixed paraffin embedded tissues, a recommendation as ready for use by the American Society of Clinical Oncology Breast Cancer Tumor Markers Update Committee, a continuous rather than dichotomous algorithm, inclusion of both estrogen receptor (ER) and human epidermal growth factor receptor 2 in the mRNA profile, an ability to serve as both a prognostic and predictive test for certain hormonal and chemotherapeutic agents, demonstrated cost-effectiveness in 1 published study, and a high accrual rate for the prospective validation clinical trial (Trial Assigning Individualized Options for Treatment Rx). The MammaPrint assay has the advantages of a 510(k) clearance by the US Food and Drug Administration, a larger gene number which may enhance further utility, and the potentially wider patient eligibility including lymph node-positive, ER-negative, and younger patients being accrued into the prospective trial (the Microarray in Node-negative Disease may Avoid ChemoTherapy). A number

  14. Neutropenic enterocolitis in children and young adults with cancer: prognostic value of clinical and image findings.

    PubMed

    Rizzatti, Marcelo; Brandalise, Silvia Regina; de Azevedo, Amilcar Cardoso; Pinheiro, Vitória Régia Pereira; Aguiar, Simone dos Santos

    2010-09-01

    Intensive chemotherapy regimens can result in severe toxicities, particularly those that involve the digestive systems, leading to morbidity and mortality in this group of patients. Acute enterocolitis can be a frequent complication. The authors performed a retrospective review or patients treated at their institution to ascertain the prognostic value of the clinical symptoms and signs of acute enterocolitis, the corresponding abdominal ultrasonographic findings, and the impact of previous chemotherapy. Amongst 1159 patients with cancer treated at the Centro Infantil Boldrini from 2003 to 2007, 188 (16.2%) patients had 1 or more episode of enterocolitis. An intestinal wall thickness of >or=3 mm on ultrasound was considered diagnostic of enterocolitis. There were 231 episodes of enterocolitis with a death rate of 11.7%. Previous therapy with cytarabine and the presence of abdominal distention affected survival. An intestinal wall thickness of >or=10 mm in the ultrasonographic examination was associated with greater mortality. In multivariate analysis, age, gender, tumor type, degree of neutropenia, intestinal wall thickness, and number of intestinal segments were not statistically significant difference. In children and young adults with cancer and enterocolitis, the clinical findings of 4 or more symptoms and presence of abdominal distention were associated with higher risk of death. Use of cytarabine and an intestinal wall thickness of >or=10 mm were associated with a higher death rate.

  15. Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis.

    PubMed

    Zou, Xue-Lin; Wang, Chun; Liu, K E; Nie, Wen; Ding, Zhen-Yu

    2015-05-01

    Osteopontin (OPN) plays an important role in the progression and metastasis of cancer. However, the role of OPN as a prognostic factor in non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to investigate the association between OPN expression and prognosis in patients with NSCLC using a meta-analysis. Based on PubMed, Ovid Medline, Embase, ISI, ScienceDirect and SpringerLink databases, related articles published prior to January, 2013 were collected. A meta-analysis was conducted to investigate the association of OPN expression with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) was used to assess the strength of this association. A total of 6 studies, including 776 patients, were found to be eligible for the meta-analysis. No heterogeneity was observed in OS or PFS, whereas low OPN expression was found to be correlated with better OS (HR=0.57, 95% CI: 0.46-0.70) and PFS (HR=0.62, 95% CI: 0.49-0.77). This meta-analysis demonstrated an association of OPN with poor prognosis in NSCLC patients. However, prospective studies are required to confirm these findings.

  16. MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer

    PubMed Central

    Gemoll, Timo; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Habermann, Jens K.

    2015-01-01

    DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for direct analysis of multiple proteins in tissue sections while maintaining the cellular and molecular integrity. We compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of IMS. DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and independent validation set were used to predict ploidy status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Five peaks (m/z 2,395 and 4,977 for diploid vs. aneuploid comparison as well as m/z 3,376, 6,663, and 8,581 for normal mucosa vs. carcinoma comparison) were significant in both SNN and ROC analysis. Among these, m/z 4,977 was identified as thymosin beta 4 (Tβ-4). Tβ-4 was subsequently validated in clinical samples using a tissue microarray to predict overall survival in colon cancer patients. PMID:26556858

  17. Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review.

    PubMed

    Li, Yanliang; Lyu, Zhongchuan; Zhao, Lixin; Cheng, Hong; Zhu, Dongyuan; Gao, Yongsheng; Shang, Xiuwan; Shi, Huaijie

    2015-03-01

    The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

  18. Correlation of cytokines and inducible nitric oxide synthase expression with prognostic factors in ovarian cancer.

    PubMed

    Martins Filho, Agrimaldo; Jammal, Millena Prata; Côbo, Eliângela de Castro; Silveira, Thales Parenti; Adad, Sheila Jorge; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2014-01-01

    The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients.

  19. 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.

  20. Bioelectrical impedance phase angle as a prognostic indicator of survival in head-and-neck cancer

    PubMed Central

    Władysiuk, M.S.; Mlak, R.; Morshed, K.; Surtel, W.; Brzozowska, A.; Małecka-Massalska, T.

    2016-01-01

    Background Phase angle could be an alternative to subjective global assessment for the assessment of nutrition status in patients with head-and-neck cancer. Methods We prospectively evaluated a cohort of 75 stage iiib and iv head-and-neck patients treated at the Otolaryngology Department, Head and Neck Surgery, Medical University of Lublin, Poland. Bioelectrical impedance analysis was performed in all patients using an analyzer that operated at 50 kHz. The phase angle was calculated as reactance divided by resistance (Xc/R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Results Median overall survival in the cohort was 32.0 months. At the time of analysis, 47 deaths had been recorded in the cohort (62.7%). The risk of shortened overall survival was significantly higher in patients whose phase angle was less than 4.733 degrees than in the remaining patients (19.6 months vs. 45 months, p = 0.0489; chi-square: 3.88; hazard ratio: 1.8856; 95% confidence interval: 1.0031 to 3.5446). Conclusions Phase angle might be prognostic of survival in patients with advanced head-and-neck cancer. Further investigation in a larger population is required to confirm our results. PMID:27803609

  1. Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility.

    PubMed

    Ravelli, Andrea; Roviello, Giandomenico; Cretella, Daniele; Cavazzoni, Andrea; Biondi, Alessandra; Cappelletti, Maria Rosa; Zanotti, Laura; Ferrero, Giuseppina; Ungari, Marco; Zanconati, Fabrizio; Bottini, Alberto; Alfieri, Roberta; Petronini, Pier Giorgio; Generali, Daniele

    2017-04-01

    The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.

  2. Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis

    PubMed Central

    ZOU, XUE-LIN; WANG, CHUN; LIU, KE; NIE, WEN; DING, ZHEN-YU

    2015-01-01

    Osteopontin (OPN) plays an important role in the progression and metastasis of cancer. However, the role of OPN as a prognostic factor in non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to investigate the association between OPN expression and prognosis in patients with NSCLC using a meta-analysis. Based on PubMed, Ovid Medline, Embase, ISI, ScienceDirect and SpringerLink databases, related articles published prior to January, 2013 were collected. A meta-analysis was conducted to investigate the association of OPN expression with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) was used to assess the strength of this association. A total of 6 studies, including 776 patients, were found to be eligible for the meta-analysis. No heterogeneity was observed in OS or PFS, whereas low OPN expression was found to be correlated with better OS (HR=0.57, 95% CI: 0.46–0.70) and PFS (HR=0.62, 95% CI: 0.49–0.77). This meta-analysis demonstrated an association of OPN with poor prognosis in NSCLC patients. However, prospective studies are required to confirm these findings. PMID:26137280

  3. Prognostic value of a cell cycle progression score for men with prostate cancer.

    PubMed

    Cuzick, Jack

    2014-01-01

    A new prognostic score called the cell cycle progression or CCP score has been evaluated for predicting outcome in men with prostate cancer. The score is based on 31 cell cycle progression genes and 15 housekeeper control genes. Results on 5 cohorts have been reported. In all cases the CCP score was strongly predictive of outcome both in univariate models and in multvariate models incorporating standard factors such as Gleason grade, PSA levels and extent of disease. Two cohorts evaluated patients managed by active surveillance where the outcome was death from prostate cancer, two cohorts examined patients treated by radical prostatectomy where biochemical recurrence was the primary endpoint, and one smaller cohort looked at patients treated with radiotherapy where again biochemical recurrence was used as the endpoint. In all cases a unit change in CCP score was associated with an approximate doubling of risk of an event. These data provide strong event to support use of the CCP score to help guide clinical management.

  4. Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer

    PubMed Central

    Pierga, J-Y; Mouret, E; Diéras, V; Laurence, V; Beuzeboc, P; Dorval, T; Palangié, T; Jouve, M; Vincent-Salomon, A; Scholl, S; Extra, J-M; Asselain, B; Pouillart, P

    2000-01-01

    Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2–T3, N0–N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46.5% of patients. Patients with ≥ eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with ≥ eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076657

  5. A Systematic Review of Clinical Outcomes and Prognostic Factors for Patients Undergoing Surgery for Spinal Metastases Secondary to Breast Cancer

    PubMed Central

    Sciubba, Daniel M.; Goodwin, C. Rory; Yurter, Alp; Ju, Derek; Gokaslan, Ziya L.; Fisher, Charles; Rhines, Laurence D.; Fehlings, Michael G.; Fourney, Daryl R.; Mendel, Ehud; Laufer, Ilya; Bettegowda, Chetan; Patel, Shreyaskumar R.; Rampersaud, Y. Raja; Sahgal, Arjun; Reynolds, Jeremy; Chou, Dean; Weber, Michael H.; Clarke, Michelle J.

    2015-01-01

    Study Design  Review of the literature. Objective  Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. Methods  We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. Results  The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. Conclusion  With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI. PMID:27433433

  6. Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan.

    PubMed

    Liu, Shyun-Yeu; Lu, Chin-Li; Chiou, Chang-Ta; Yen, Ching-Yu; Liaw, Gwo-An; Chen, Yi-Chun; Liu, Yu-Chi; Chiang, Wei-Fan

    2010-04-01

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers in geographic regions where betel quid (BQ) chewing is prevalent; OSCC is an extremely malignant neoplasm whose prognostic factors are multiple and complex. The purpose of this study was to assess clinicopathological prognostic factors and treatment outcomes in 698 consecutive OSCC patients who had undergone surgery as the primary treatment in an area with a high prevalence of both betel quid chewing and tobacco smoking. The prognostic factors were predicted using Cox's proportional-hazards regression model, and the survival rate was calculated using Kaplan-Meier analysis. The median followup for all patients was 44 months. The 5-year cumulative overall, disease-specific, and locoregional control survival rates were 61%, 62%, and 46%, respectively. Multivariate analysis showed that the lower level of nodal metastasis, advanced stage, tumor thickness >7 mm, and treatment failures were independent risk factors of overall survival. Furthermore, history of alcohol drinking, lower level of nodal metastasis, advanced stage, poor cell differentiation, and treatment failures were independent predictors of poor disease-specific survival. However, we did not find any significant factor that affected locoregional recurrence. Due to the high frequencies of locoregional recurrence and second primary cancer, our findings emphasize that aggressive surgical excision, adjuvant treatments according to clinicopathological prognostic factors and close surveillance are important to the survival of OSCC patients in an area with a high prevalence of betel quid chewing and tobacco smoking.

  7. Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer.

    PubMed

    Fedyanin, Mikhail; Anna, Popova; Elizaveta, Polyanskaya; Sergei, Tjulandin

    2017-01-01

    In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions. The following markers are typically considered as markers of colorectal adenocarcinoma stem cells: CD133, CD144, CD24, CD166, CD44, CD29, ALDH1, LGR5, and CXCR4. However, data on the role of cancer stem cells in the process of colorectal cancer progression, their prognostic and predictive role are lacking. Researches on the phenotype, molecular and functional properties of this tumor cell subpopulation in both primary site and metastases of colorectal cancer are of great interest because they can allow developing new diagnostic and therapeutic strategies in the future.

  8. Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

    PubMed Central

    Li, Tao; Zheng, Hong-Mei; Deng, Nai-Mei; Jiang, Ying-Jian; Wang, Jiang; Zhang, Dian-Liang

    2017-01-01

    AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A χ2 test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (χ2 = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC. PMID:28293092

  9. Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

    PubMed Central

    Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

    2015-01-01

    To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

  10. Joint prognostic effect of obesity and chronic systemic inflammation in metastatic colorectal cancer

    PubMed Central

    Shah, Manasi S.; Fogelman, David R.; Raghav, Kanwal Pratap Singh; Heymach, John V.; Tran, Hai T.; Jiang, Zhi-Qin; Kopetz, Scott; Daniel, Carrie R.

    2015-01-01

    BACKGROUND Obesity is strongly linked with chronic systemic inflammation, and each has been linked with progression and survival in colorectal cancer (CRC). We investigated the joint prognostic effects of obesity and circulating cytokines in metastatic CRC (mCRC), an understudied patient group. METHODS In 242 chemotherapy naïve mCRC patients, we measured a multiplex cytokine panel and abstracted clinical-pathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. RESULTS In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS [hazard ratio (HR) and 95% confidence interval (CI) for above vs. below (ref) knot point: 2.5 (1.7, 3.7); 1.9 (1.3, 2.7); and 2.2 (1.6, 3.1), respectively; all P<0.001]. Obesity (BMI>30) was not associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4- and 5-fold risk of death in obese patients, as compared to a 2-fold risk of death in non-obese patients (P-interaction= 0.06 and 0.04, respectively). Similar results emerged from joint effects analysis, where obese patients with high IL-8 (or LDH) experienced the highest risk of death. CONCLUSIONS Although obesity itself was not independently associated with survival in mCRC patients, the adverse prognostic importance of LDH and IL-8 was enhanced in obese patients. PMID:25975416

  11. Treatment outcome and prognostic factor of CO2 laser cordectomy for early glottic cancer

    NASA Astrophysics Data System (ADS)

    Chung, Phil-Sang; Lee, Sang Joon

    2012-02-01

    Objectives: Laser cordectomy is very popular nowadays and become one of the treatments of choice for early glottis carcinoma. Transoral laser microsurgery has many advantages comparing conventional open surgery or radiation therapy. In this study, we examined the oncologic results of laser cordectomy for early glottic cancer and analyzed the prognostic impact on the survival of the several tumor-related and treatment-related factors. Methods: Patients who were diagnosed as early glottic squamous cell carcinoma, treated by laser cordectomy with curative intent were analyzed. Patients with preivous radiation therapy were included. From June 1988 to March 2005, 202 patients from five hospitals were analyzed (174 T1, 28 T2). Results: Five-year overall survival and disease-free survival were 98.4% and 84.9%. Twenty two patients developed local recurrence. Total laryngectomy was done in 6 patients and laryngeal preservation rate was 97%. Recurrence was higher in the patients with anterior commissure involvement (9/39) than without anterior commissure involvement (13/163). Recurrence was higher in T1b (4/15) than T1a (13/159). Previous radiation was also highly related to the recurrence (7/20 vs 15/182). Twenty patients with local recurrence after radiation therapy were treated by salvage laser cordectomy. Of them, 7 patients developed local recurrence and 5 year disease-free survival was 57%. Complication was rare with one case of hemorrhage. Tracheotomy was not necessary in all patients. Conclusions: Laser cordectomy for early glottic carcinoma showed high survival, laryngeal preservation rate and low complication rate. The prognostic factors were anterior commissure involvement, both vocal fold involvement and previous radiotherapy.

  12. Outcome and Prognostic Factors in Endometrial Stromal Tumors: A Rare Cancer Network Study

    SciTech Connect

    Schick, Ulrike; Bolukbasi, Yasmin; Thariat, Juliette; Abdah-Bortnyak, Roxolyana; Kuten, Abraham; Igdem, Sefik; Caglar, Hale; Ozsaran, Zeynep; Loessl, Kristina; Schleicher, Ursula; Zwahlen, Daniel; Villette, Sylviane; Vees, Hansjoerg

    2012-04-01

    Purpose: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). Methods and Materials: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. Results: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age ({<=}60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). Conclusion: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.

  13. Dual specificity phosphatase 5 is a novel prognostic indicator for patients with advanced colorectal cancer

    PubMed Central

    Yan, Xuebing; Liu, Liguo; Li, Hao; Huang, Linsheng; Yin, Mingming; Pan, Cheng; Qin, Huanlong; Jin, Zhiming

    2016-01-01

    Dual specificity phosphatase 5 (DUSP5) is a negative regulator of Mitogen-activated protein kinase (MAPK) signaling pathway and has recently been identified as a tumor suppressor in several human malignancies. However, its clinical significance in colorectal cancer (CRC) remains unclear. In this study, we aimed to investigate the potential utility of DUSP5 as a novel biomarker for progression indication and chemotherapy benefit in CRC patients. Through quantitative real time-polymerase chain reaction and western blot, we determined that DUSP5 expression is dramatically lower in CRC tissues than that in matched normal tissues. The statistical analysis based on immunohistochemistry revealed that DUSP5 expression is significantly correlated with tumor differentiation, TNM stage, lymph node metastasis and distant metastasis. For the whole study cohort, patients with high DUSP5 expression had a better CRC-specific and disease-free survival than those with low DUSP5 expression and DUSP5 expression is an independent prognostic factor for patient survival. In subgroup analysis, DUSP5 has no prognostic significance in low-risk stage II patients, but could predict treatment response in high-risk stage II and stage III/IV patients who received standard FOLFOX chemotherapy scheme. Finally, the correlation analysis suggested that DUSP5 expression is associated with Epithelial-to-Mesenchymal Transition (EMT) phenotype in CRC tissues, suggesting that downregulated DUSP5 may contribute to poor prognosis partly by involving EMT. Taken together, our study proposes that DUSP5 is a promising biomarker for predicting CRC progression and advanced patients with high DUSP5 expression appear to benefit from standard FOLFOX chemotherapy scheme. PMID:27822421

  14. Prognostic utility of molecular factors by age at diagnosis of colorectal cancer

    PubMed Central

    McCleary, Nadine J; Sato, Kaori; Nishihara, Reiko; Inamura, Kentaro; Morikawa, Teppei; Zhang, Xuehong; Wu, Kana; Yamauchi, Mai; Kim, Sun A; Sukawa, Yasutaka; Mima, Kosuke; Qian, Zhi Rong; Fuchs, Charles S; Ogino, Shuji; Meyerhardt, Jeffrey A

    2016-01-01

    PURPOSE We hypothesized that adverse prognostic associations of specific tumor molecular factors vary by patient age at colorectal cancer (CRC) diagnosis. EXPERIMENTAL DESIGN We examined the prognostic associations and interactions by age at CRC diagnosis (<60 vs. 60–74 vs. ≥75 years old) of key molecular factors – CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and PIK3CA mutations, and nuclear CTNNB1 expression status – on CRC-specific survival and overall survival, utilizing 1280 incident CRC cases (median age 69 years, range 38–91 years) within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. RESULTS MSI-high was associated with better survival while BRAF mutation was associated with worse survival, but these associations did not appreciably differ by age group. Status of CIMP, KRAS mutation, or PIK3CA mutation was not associated with prognosis regardless of age. Nuclear CTNNB1 expression was associated with a trend toward worse prognosis among older adults (age ≥75) [multivariate hazard ratio (HR), 1.67; 95% confidence interval (CI) 0.89 to 3.13 (for CRC-specific survival); multivariate HR 1.44; 95% CI 0.93 to 2.24 (for overall survival)] but not among younger patients, and there was a statistically significant interaction by age (p-interaction=0.03 for CRC-specific survival; p-interaction=0.007 for overall survival). CONCLUSIONS Tumor nuclear CTNNB1 expression may be associated with higher mortality among older CRC patients but not among younger patients. Our findings need to be confirmed in independent datasets. Detailed exploration of tumor molecular signatures in older CRC patients in large populations is warranted. PMID:26490308

  15. Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database

    PubMed Central

    Li, Mu; Dai, Chen-Yang; Wang, Yu-Ning; Chen, Tao; Wang, Long; Yang, Ping; Xie, Dong; Mao, Rui; Chen, Chang

    2016-01-01

    Background Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. Results Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64–0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54–0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53–0.93, p = 0.015). Methods We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. Conclusions Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors. PMID:27780931

  16. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy.

    PubMed Central

    Sugarbaker, P H; Jablonski, K A

    1995-01-01

    OBJECTIVE: A treatment plan to be used in patients with peritoneal carcinomatosis was devised and tested as a Phase II study. BACKGROUND: Peritoneal carcinomatosis from appendical or colorectal cancer has been regarded as a fatal clinical entity. Treatment protocols have not been reported previously. METHODS: The authors used cytoreductive surgery and intraperitoneal chemotherapy to treat 181 consecutive patients with peritoneal carcinomatosis. There were 51 patients with colorectal cancer and 130 patients with appendiceal cancer. Mean follow-up is 24 months, with a range of 0 to 149 months. RESULTS: Clinical features that showed prognostic significance included appendiceal versus colorectal primary tumors (p = 0.0001), grade 1 versus grades 2 and 3 histopathology (p = 0.0003), complete versus incomplete cytoreductions (p = 0.0001), lymph node-negative versus lymph node-positive primary tumors (p = 0.0001), and volume of peritoneal carcinomatosis present preoperatively for colon cancer (p = 0.0006). Features with no statistical prognostic significance included preoperative tumor volume for appendiceal cancer, age, sex, number of cycles of chemotherapy, operative time, complications, blood loss, and institution providing treatment. From these prognostic features, four prognostic groups were identified, and 3-year survival was estimated by the product-limit survival method. Group I patients (n = 76) were those with grade 1 histology, no lymph node metastases, and complete cytoreductions (survival at 3 years = 99%). Group II patients (n = 23) were those with grade 2 or 3 histology, no lymph node metastases, and complete cytoreductions (65%). Group III patients (n = 24) had any histology, lymph node metastases, and complete cytoreductions (66%). Group IV patients (n = 58) had incomplete cytoreductions (20%). PMID:7857141

  17. High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

    PubMed Central

    Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

    2017-01-01

    Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

  18. [Clinical implications of the "war against cancer"].

    PubMed

    Rojas Miranda, Daniela; Fernández González, Loreto

    2015-03-01

    This article discusses the origin and implications of the "war on cancer" metaphor. Commonly present in mass media, the "war on cancer" notion circulates also among patients, their loved ones, their support networks, and oncological multidisciplinary teams. In our view when cancer is uprooted of its illness status, and conceptualized as an "enemy", myths about disease and those who suffer it (especially the idea of psychogenesis) are strengthened. Two topics in which the war metaphor is particularly problematic in the clinical context, are analyzed in depth. The first one is the relationship between the oncologic patient and his or her loved ones and support networks. When patients are insistently prompted to fight the disease and think positive, the expression of emotions associated to the adaptive process of receiving a diagnosis of cancer may be inhibited. Secondly, the war metaphor promotes an authoritarian view among the health teams and on the physician-patient relationship, undermining the patent's autonomy in the decision-making process, which may affect his global quality of life. Also, it encourages emotional isolation, concealment of psychiatric symptoms and conspiracies of silence. It is concluded that public policies to avoid the "war on" notion are required. Instead, education of the general population about wrong beliefs about cancer should be encouraged.

  19. CDGSH iron sulfur domain 2 activates proliferation and EMT of pancreatic cancer cells via Wnt/β-catenin pathway and has prognostic value in human pancreatic cancer.

    PubMed

    Yang, Yang; Bai, Yuan-Song; Wang, Qing

    2016-10-26

    Recently, increasing evidence has shown that CDGSH iron sulfur domain2 (CISD2) is involved in the initiation and metastasis of several cancers. However, the evidence of its potential role in pancreatic cancer is still lacking. In our present study, CISD2 was found to be increased in pancreatic cancer samples and multiple cell lines. Moreover, statistical analysis revealed that a high level of CISD2 was related to advanced clinical stage, advanced T-stage, positive vascular invasion, positive distant metastasis, and larger tumor size. In addition, multivariate analysis suggests that CISD2 was an independent prognostic factor in pancreatic cancer. Importantly, downregulation of CISD2 was capable of inhibiting the survival and growth of pancreatic cancer cells. Mechanistic study showed that inactivation of the Wnt/β-catenin pathway contributed to the CISD2 deficit-induced death of pancreatic cancer cells. Furthermore, we showed that CISD2 silencing significantly inhibited EMT via the Wnt/β-catenin pathway. Finally, in nude mice, CISD2 deficit suppressed the tumorigenesis of pancreatic cancer cells. Collectively, our study demonstrated that CISD2 could be an independent prognostic factor for pancreatic cancer and suggested that the CISD2/Wnt/β-catenin pathway contributes to the proliferation of pancreatic cancer cells and EMT, hinting at a novel promising molecular target in the therapeutic strategy for pancreatic cancer.

  20. Feeling too hot or cold after breast cancer: Is it just a nuisance or a potentially important prognostic factor?

    PubMed Central

    KOKOLUS, KATHLEEN M.; HONG, CHI-CHEN; REPASKY, ELIZABETH A.

    2010-01-01

    There is widespread recognition among both patients and caregivers that breast cancer patients often experience debilitating deficiencies in their ability to achieve thermal comfort, feeling excessively hot or cold under circumstances when others are comfortable. However, this symptom receives little clinical or scientific attention beyond identification and testing of drugs that minimise menopausal-like symptoms. Could some of these symptoms represent an important prognostic signal? Could thermal discomfort be among other cytokine-driven sickness behaviour symptoms seen in many breast cancer patients? While the literature reveals a strong link between treatment for breast cancer and some menopausal vasomotor symptoms (e.g. hot flashes also known as “hot flushes”), there is little data on quantitative assessment of severity of different types of symptoms and their possible prognostic potential. However, recent, intriguing studies indicating a correlation between the presence of hot flashes and reduced development of breast cancer recurrence strongly suggests that more study on this topic is needed. In comparison to reports on the phenomenon of breast cancer-associated hot flashes, there is essentially no scientific study on the large number of women who report feeling excessively cold after breast cancer treatment. Since similar acquired thermal discomfort symptoms can occur in patients with cancers other than breast cancer, there may be as yet unidentified cancer – or treatment-driven factor related to temperature dysregulation. In general, there is surprisingly little information on the physiological relationship between body temperature regulation, vasomotor symptoms, and cancer growth and progression. The goal of this article is twofold: (1) to review the scientific literature egarding acquired deficits inthermoregulation among breast cancer survivors and (2) to propose some speculative ideas regarding the possible basis for thermal discomfort among some

  1. Feeling too hot or cold after breast cancer: is it just a nuisance or a potentially important prognostic factor?

    PubMed

    Kokolus, Kathleen M; Hong, Chi-Chen; Repasky, Elizabeth A

    2010-01-01

    There is widespread recognition among both patients and caregivers that breast cancer patients often experience debilitating deficiencies in their ability to achieve thermal comfort, feeling excessively hot or cold under circumstances when others are comfortable. However, this symptom receives little clinical or scientific attention beyond identification and testing of drugs that minimise menopausal-like symptoms. Could some of these symptoms represent an important prognostic signal? Could thermal discomfort be among other cytokine-driven sickness behaviour symptoms seen in many breast cancer patients? While the literature reveals a strong link between treatment for breast cancer and some menopausal vasomotor symptoms (e.g. hot flashes also known as "hot flushes"), there is little data on quantitative assessment of severity of different types of symptoms and their possible prognostic potential. However, recent, intriguing studies indicating a correlation between the presence of hot flashes and reduced development of breast cancer recurrence strongly suggests that more study on this topic is needed. In comparison to reports on the phenomenon of breast cancer-associated hot flashes, there is essentially no scientific study on the large number of women who report feeling excessively cold after breast cancer treatment. Since similar acquired thermal discomfort symptoms can occur in patients with cancers other than breast cancer, there may be as yet unidentified cancer- or treatment-driven factor related to temperature dysregulation. In general, there is surprisingly little information on the physiological relationship between body temperature regulation, vasomotor symptoms, and cancer growth and progression. The goal of this article is twofold: (1) to review the scientific literature regarding acquired deficits in thermoregulation among breast cancer survivors and (2) to propose some speculative ideas regarding the possible basis for thermal discomfort among some of

  2. Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers.

    PubMed

    Sänger, N; Engels, K; Graf, A; Ruckhäberle, E; Effenberger, K E; Fehm, T; Holtrich, U; Becker, S; Karn, T

    2014-11-01

    Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) invasive breast cancer cases and found no significant differences in age, receptor status of ER, PR, and HER2, and the use of radiotherapy. Interestingly, the proportion of disseminated tumor cells (DTC) did also not significantly differ between DCIS and invasive cases (p = 0.57). A negative PR status was associated with the detection of DTCs (p = 0.026). We then compared relationships of clinical parameters and biomarkers with patients' prognosis in 43 DCIS and 40 small invasive tumors ≤ 5 mm (T1a). ER negativity was associated with shorter relapse free survival in the complete cohort (p = 0.004) and showed a trend in both subgroups (p = 0.053 for DCIS and p = 0.046 for T1a, respectively). In conclusion, we found markedly similar properties of both DCIS and small invasive breast cancers with respect to the distribution of several parameters as well as to the prognostic value of biomarkers. DCIS with a luminal phenotype seem to be characterized by a favourable prognosis.

  3. Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer

    PubMed Central

    Yang, Shu; Zhang, Yalong; Pu, Honglei; Fu, Fangqiu; Huang, Yan; Wu, Hai; Li, Tao; Li, Yao

    2016-01-01

    Prostate cancer (PCa) is a leading cause of mortality among males. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE. Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples. Ten lncRNAs were selected for further validation by examining their expressions in LNCaP cells under DHT stimulation, and in PCa samples and cell lines. Among them, RP1-4514.2, LINC01138, SUZ12P1 and KLKP1 were validated as directly AR-targeted lncRNAs by ChIP-PCR. Then we conducted a bioinformatic analysis to identify lncRNAs as putative prognostic and therapeutic targets by using TCGA data. Three androgen-responsive lncRNAs, LINC01138, SUZ12P1 and SNHG1 showed association with gleason score and pT-stage. The biological functions of LINC01138 and SUZ12P1 were also evaluated, both lncRNAs promoted the proliferation and inhibited apoptosis of PCa. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant PCa. PMID:27556357

  4. Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer.

    PubMed

    Ma, Cynthia X; Bose, Ron; Ellis, Matthew J

    2016-01-01

    The estrogen-dependent nature of breast cancer is the fundamental basis for endocrine therapy. The presence of estrogen receptor (ER), the therapeutic target of endocrine therapy, is a prerequisite for this therapeutic approach. However, estrogen-independent growth often exists de novo at diagnosis or develops during the course of endocrine therapy. Therefore ER alone is insufficient in predicting endocrine therapy efficacy. Several RNA-based multigene assays are now available in clinical practice to assess distant recurrence risk, with majority of these assays evaluated in patients treated with 5 years of adjuvant endocrine therapy. While MammaPrint and Oncotype Dx are most predictive of recurrence risk within the first 5 years of diagnosis, Prosigna, Breast Cancer Index (BCI), and EndoPredict Clin have also demonstrated utility in predicting late recurrence. In addition, PAM50, or Prosigna, provides further biological insights by classifying breast cancers into intrinsic molecular subtypes. Additional strategies are under investigation in prospective clinical trials to differentiate endocrine sensitive and resistant tumors and include on-treatment Ki-67 and Preoperative Endocrine Prognostic Index (PEPI) score in the setting of neoadjuvant endocrine therapy. These biomarkers have become important tools in clinical practice for the identification of low risk patients for whom chemotherapy could be avoided. However, there is much work ahead toward the development of a molecular classification that informs the biology and novel therapeutic targets in high-risk disease as chemotherapy has only modest benefit in this population. The recognition of somatic mutations and their relationship to endocrine therapy responsiveness opens important opportunities toward this goal.

  5. Ki-67 as a prognostic marker according to breast cancer molecular subtype

    PubMed Central

    Soliman, Nahed A.; Yussif, Shaimaa M.

    2016-01-01

    Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed. Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Follow-up ranged from 32 months up to 6 years. Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative (TN), respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in 34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than 15% (P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15% (P = 0.000). Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients. PMID:28154782

  6. Prognostic assessment of apoptotic gene polymorphisms in non-small cell lung cancer in Chinese

    PubMed Central

    Cao, Songyu; Wang, Cheng; Huang, Xinen; Dai, Juncheng; Hu, Lingmin; Liu, Yao; Chen, Jiaping; Ma, Hongxia; Jin, Guangfu; Hu, Zhibin; Xu, Lin; Shen, Hongbing

    2013-01-01

    Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypothesis, we selected 38 potentially functional single nucleotide polymorphisms (SNPs) from 12 genes (BAX, BCL2, BID, CASP3, CASP6, CASP7, CASP8, CASP9, CASP10, FAS, FASLG and MCL1) involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer (NSCLC) patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival (P < 0.05). After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC (BID rs8190315: P = 0.003; CASP9 rs4645981: P = 0.007 and FAS rs1800682: P = 0.016). A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG (adjusted HR = 0.65, 95% CI: 0.49-0.88), CASP9 rs4645981 AA (HR = 0.22, 95% CI: 0.07-0.69) and FAS rs1800682 GG (adjusted HR = 0.67, 95% CI: 0.46-0.97). Time-dependent receptor operation curve (ROC) analysis revealed that the area under curve (AUC) at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not significantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population. PMID:23720679

  7. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer

    SciTech Connect

    Leoutsakou, Theoni; Talieri, Maroulio; Scorilas, Andreas . E-mail: ascorilas@biol.uoa.gr

    2006-06-02

    The SR-related-CTD-associated-factors (SCAFs) have the ability to interact with the C-terminal domain of the RNA polymerase II, linking this way transcription to splicing. SRA1 (SR-A1) gene, encoding for a human high-molecular weight SCAF protein, is located on chromosome 19, between the IRF3 and the R-RAS oncogene and it has been demonstrated from members of our group that SRA1 is constitutively expressed in most of the human tissues, while it is overexpressed in a subset of ovarian tumors. In this study, we examine the expression of SRA1 gene in 111 ovarian malignant tissues and in the human ovarian carcinoma cell lines OVCAR-3, TOV21-G, and ES-2, using a semi-quantitative RT-PCR method. SRA1 gene was overexpressed in 61/111 (55%) of ovarian carcinomas. This higher expression was positively associated to the size of the tumor (p < 0.001), the grade and the stage of the disease (p = 0.003 and p = 0.006, respectively), and the debulking success (p < 0.001). Kaplan-Meier survival analysis revealed that lower SRA1 expression increases the probability of both the longer overall and the progression free survival of the patients. Multivariate Cox regression analysis revealed that SRA1 may be used as an independent prognostic biomarker in ovarian cancer. Our results suggest that SRA1 is associated with cancer progression and may possibly be characterized as a new marker of unfavorable prognosis for ovarian cancer.

  8. Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients

    PubMed Central

    Kristensen, Gunnar; Embleton, Andy; Adusei, Cybil; Barretina-Ginesta, Maria Pilar; Beale, Philip

    2017-01-01

    Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n = 207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n = 91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation. PMID:28293063

  9. Predictive and Prognostic Analysis of PIK3CA Mutation in Stage III Colon Cancer Intergroup Trial

    PubMed Central

    Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Niedzwiecki, Donna; Saltz, Leonard B.; Mayer, Robert J.; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Mowat, Rex B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2013-01-01

    Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P interaction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P interaction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. PMID:24231454

  10. Studies in prognostic factors relating to chemotherapy for advanced gastric cancer.

    PubMed

    Lavin, P T; Bruckner, H W; Plaxe, S C

    1982-11-15

    The prognostic value of pretreatment information relating to prior treatment, demography, physical status, symptoms, disease involvement, pathologic, immunologic, and clinical chemistries were analyzed for a series of 322 patients with advanced gastric cancer. All patients received chemotherapy upon entry into Gastrointestinal Tumor Study Group protocols which were active between 1975 and 1978. Multivariate models were used to study relationships between prognostic factors and survival for all patients and objective tumor resonse for a subset of 137 patients with measurable disease. The initial performance status was a leading determinant of survival (P less than 0.0001). In addition, new summary measures relating to blood chemistries (P less than 0.01) and differential counts (P less than 0.001) were shown to influence patient survival. Blood chemistry parameters included SGOT, total serum protein, and total direct bilirubin while differential counts included absolute granulocytes, lymphocytes, and monocytes. Thus, the initial performance status, measurable disease status, blood chemistries, and differential counts are recommended as stratification factors in the design and analysis of trials involving patients with advanced gastric cancer. The initial performance status was examined in relation to other pretreatment data. The performance status at study entry correlated independently with the degree of weight loss (P less than 0.001), blood chemistries (P less than 0.01), differential counts (P less than 0.05), and peritoneal metastases (P less than 0.05). The measurable and nonmeasurable subgroups were compared with respect to baseline characteristics. Patients with measurable disease had more liver metastases (56 versus 35%) and less peritoneal metastases (76 versus 49%) than patients with nonmeasurable disease. Controlling for the imbalance in liver and peritoneal metastases, the presence of measurable disease was less favorable than nonmeasurable disease with

  11. NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells

    PubMed Central

    Zhong, Ying; Shen, Songjie; Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Xu, Yali; Zhang, Shu; Liu, Xu; Sun, Qiang

    2016-01-01

    Recently, the human gene NOTCH1 has been found to be implicated in cancer cell metastasis and the maintenance of cancer stem cells. However, for breast cancer in particular, an association between NOTCH1 levels and metastasis has not been determined. In this study, we investigated the expression status and correlation of NOTCH1 with clinically important factors related to metastasis and the cancer stem cell marker ALDH1. NOTCH1 and ALDH1 levels in 115 tumor tissues from primary lesions were determined by immunohistochemical staining. Most tissues were stained positive for both NOTCH1 and ALDH1, and NOTCH1 positivity was significantly associated with ALDH1 levels. NOTCH1 levels were significantly associated with TNM stage, metastasis, and triple-negative breast cancer. Moreover, both univariate and multivariate regression analyses revealed that basal-like features and NOTCH1 positivity were associated with disease-free survival as independent predictors. These analyses indicated that breast cancer patients testing positive for NOTCH1 had shorter disease-free survival. Our findings suggest that NOTCH1 may be involved in metastasis and is closely correlated with breast cancer stem cells. PMID:27853380

  12. NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells.

    PubMed

    Zhong, Ying; Shen, Songjie; Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Xu, Yali; Zhang, Shu; Liu, Xu; Sun, Qiang

    2016-01-01

    Recently, the human gene NOTCH1 has been found to be implicated in cancer cell metastasis and the maintenance of cancer stem cells. However, for breast cancer in particular, an association between NOTCH1 levels and metastasis has not been determined. In this study, we investigated the expression status and correlation of NOTCH1 with clinically important factors related to metastasis and the cancer stem cell marker ALDH1. NOTCH1 and ALDH1 levels in 115 tumor tissues from primary lesions were determined by immunohistochemical staining. Most tissues were stained positive for both NOTCH1 and ALDH1, and NOTCH1 positivity was significantly associated with ALDH1 levels. NOTCH1 levels were significantly associated with TNM stage, metastasis, and triple-negative breast cancer. Moreover, both univariate and multivariate regression analyses revealed that basal-like features and NOTCH1 positivity were associated with disease-free survival as independent predictors. These analyses indicated that breast cancer patients testing positive for NOTCH1 had shorter disease-free survival. Our findings suggest that NOTCH1 may be involved in metastasis and is closely correlated with breast cancer stem cells.

  13. Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis.

    PubMed

    Pang, Bo; Cheng, Shi; Sun, Shi-Peng; An, Cheng; Liu, Zhi-Yuan; Feng, Xue; Liu, Gui-Jian

    2014-09-01

    The phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast cancer (BCa). Sex hormone receptors (HRs), including estrogen receptor (ER) and progesterone receptor (PR) play pivotal roles in BCa. In this study, we evaluated the association between PIK3CA mutations and ER/PR expression and the prognostic role of PIK3CA mutations in BCa patients, and in particular, HR-positive BCa. Thirty-two studies involving 5719 cases of BCa obtained from database searches were examined. PIK3CA gene mutations correlated significantly with ER/PR expression (p < 0.00001) and relapse-free survival (RFS) (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98, p = 0.03) but not overall survival (OS) (HR 1.14, 95%CI 0.72-1.82, p = 0.57) in unsorted BCa patients. PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67-1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53-1.40, p = 0.55) in HR-positive BCa patients. In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients. However, the clinical implications of PIK3CA mutations may vary according to different mutant exons. And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

  14. Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Huang, Lanshan; Ren, Fanghui; Tang, Ruixue; Feng, Zhenbo; Chen, Gang

    2016-02-01

    Cyclin E is a critical regulator in cell cycle and promotes the initiation of DNA replication and centrosome duplication in late G1. The overexpression of cyclin E is common in cancers of the digestive system. However, whether cyclin E represents a prognostic biomarker in gastrointestinal cancer remains controversial. We reviewed the published literatures to clarify the association between cyclin E determined by immunohistochemistry (IHC) and survival in gastrointestinal cancer. Literatures were searched in PubMed and Cochrane Library published up to December 1, 2014. A total of 282 articles were initially identified, and 14 articles were included in this study. Meta-analysis was performed for 10 studies with a total of 1300 patients. Combined hazard risk (HR) and corresponding 95% confidence interval (CI) were calculated by random-effect model due to the heterogeneity. The quality of included studies was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies (MINORS). We found that high level of cyclin E was a predicator of poor prognosis among patients with gastrointestinal cancer (HR = 1.67, 95% CI = 1.06-2.63, P = .028). In summary, overexpression of cyclin E is associated with poor prognosis in gastrointestinal cancer and expression of cyclin E determined by IHC might be a prognostic marker for gastrointestinal cancer in clinical practice.

  15. Human leukocyte antigen (HLA)-G and cervical cancer immunoediting: a candidate molecule for therapeutic intervention and prognostic biomarker?

    PubMed

    Gimenes, Fabrícia; Teixeira, Jorge Juarez Vieira; de Abreu, André Luelsdorf Pimenta; Souza, Raquel Pantarotto; Pereira, Monalisa Wolski; da Silva, Vânia Ramos Sela; Bôer, Cinthia Gandolfi; Maria-Engler, Silvya Stuchi; Bonini, Marcelo Gialluisi; Borelli, Sueli Donizete; Consolaro, Márcia Edilaine Lopes

    2014-12-01

    While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervical cancer, suggesting complex host-virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervical cancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervical cancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis.

  16. KRAS driven expression signature has prognostic power superior to mutation status in non‐small cell lung cancer

    PubMed Central

    Nagy, Ádám; Pongor, Lőrinc Sándor; Szabó, András; Santarpia, Mariacarmela

    2016-01-01

    KRAS is the most frequently mutated oncogene in non‐small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer. We divided NSCLC patients with mutation and RNA‐seq data into KRAS mutated and wild type groups. Mann‐Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a “transcriptomic fingerprint” of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis. Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage. We generated a “surrogate signature” of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself. PMID:27859136

  17. The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

    PubMed

    Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

    2011-04-01

    The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

  18. Prognostic significance of differentially expressed miRNAs in esophageal cancer

    PubMed Central

    Hu, Yuxin; Correa, Arlene M.; Hoque, Ashraful; Guan, Baoxiang; Ye, Fei; Huang, Jie; Swisher, Stephen G.; Wu, Tsung Teh; Ajani, Jaffer A.; Xu, Xiao-chun

    2010-01-01

    Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21, and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126, and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-β2 expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell de-differentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e, and miR-200a expression were associated with shorter overall and disease-free survival in esophageal adenocarcinoma patients; however, miR-16-2, miR-30e, and miR-200a expression was not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study. PMID:20309880

  19. [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.

  20. Prognostic implications of PIK3CA amplification in curatively resected liposarcoma

    PubMed Central

    Kim, Eo Jin; Park, Kyu Hyun; Kim, Ki Hyang; Yi, Seong Yoon; Kim, Han Seong; Cho, Yong Jin; Shin, Kyoo-Ho; Ahn, Joong Bae; Hu, Hyuk; Kim, Kyung Sik; Choi, Young Deuk; Kim, Sunghoon; Lee, Young Han; Suh, Jin-Suck; Noh, Sung Hoon; Rha, Sun Young; Kim, Hyo Song

    2016-01-01

    Background We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. Patients and methods A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). Results Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. Conclusions We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma. PMID:27016421

  1. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    SciTech Connect

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  2. The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers.

    PubMed

    Jiao, Qingli; Wu, Aiguo; Shao, Guoli; Peng, Haoyu; Wang, Mengchuan; Ji, Shufeng; Liu, Peng; Zhang, Jian

    2014-09-01

    Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers.

  3. Prognostic value of genomic damage in non-small-cell lung cancer.

    PubMed

    de Juan, C; Iniesta, P; Vega, F J; Peinado, M A; Fernandez, C; Caldés, T; Massa, M J; López, J A; Sánchez, A; Torres, A J; Balibrea, J L; Benito, M

    1998-06-01

    Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC.

  4. Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

    PubMed Central

    Zhu, Jia-yu; Liu, Cheng-cheng; Wang, Liang; Zhong, Mei; Tang, Hai-lin; Wang, Hua

    2017-01-01

    The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

  5. The prognostic value of DNA ploidy and S-phase estimate in primary breast cancer: a prospective study.

    PubMed

    Dieterich, B; Albe, X; Vassilakos, P; Wieser, S; Friedrich, R; Krauer, F

    1995-09-27

    In this prospective study, the independent prognostic value of DNA ploidy in combination with the major clinico-pathological characteristics (histological grade, nodal status, tumor size, estrogen and progesterone receptor status, number of tumors, multicentricity, lympho-vascular infiltration) was evaluated in a series of 399 breast-cancer patients. The mean follow-up time was 4.5 years. The DNA content was measured using image cytometry on fresh tumor samples. The overall survival of tetraploid and slowly proliferating diploid cases was significantly different compared with that of aneuploid and rapidly proliferating diploid cases (p = 0.0002). Thus, DNA ploidy combined with S-phase estimate (DNA histogram type) appeared to be good prognostic factors. In a multivariate survival analysis, DNA histogram type was not an independent prognostic factor unless the histological grade was excluded. This effect of DNA histogram type on survival was also observed among patients with grade-I or -II tumors and patients with small tumors. In conclusion, DNA histogram type was a valuable prognostic factor in univariate analysis, and provided independent complementary information for patients considered at low or intermediate risk by classical pathological findings.

  6. External validation of a prognostic model predicting overall survival in metastatic castrate-resistant prostate cancer patients treated with abiraterone.

    PubMed

    Ravi, Praful; Mateo, Joaquin; Lorente, David; Zafeiriou, Zafeiris; Altavilla, Amelia; Ferraldeschi, Roberta; Sideris, Spyridon; Grist, Emily; Smith, Alan; Wong, Sophia; Bianchini, Diletta; Attard, Gerhardt; de Bono, Johann S

    2014-07-01

    A prognostic model was derived from the population of the COU-AA-301 phase 3 trial for metastatic castrate-resistant prostate cancer patients treated with abiraterone after docetaxel, and it stratifies patients into three risk groups based on clinical parameters. We validated this model in an independent cohort of patients treated with abiraterone after docetaxel outside a clinical trial (group A; n=94) and explored its utility in patients treated with abiraterone in the prechemotherapy setting (group B; n=64). For group A, median overall survival (mOS) was significantly different across the three prognostic groups (good: n=39, mOS: 21.8 mo; intermediate: n=44, mOS: 10.6 mo; poor: n=7, mOS: 6.8 mo; p<0.001; area under the curve [AUC]: 0.71). Analysis of group B confirmed the ability of the model to prognosticate for survival in the prechemotherapy setting: (good: n=44, mOS: 45.6 mo; intermediate or poor: n=20, mOS: 34.5 mo; p=0.042; AUC: 0.61). These results serve to validate the prognostic model in an independent population treated with abiraterone after docetaxel and support clinical implementation of the score. Calibration of the model was poorer in patients receiving abiraterone prechemotherapy. Prospective evaluation of this model in clinical trials is needed.

  7. Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters.

    PubMed

    Grinberg, Marianna; Djureinovic, Dijana; Brunnström, Hans Rr; Mattsson, Johanna Sm; Edlund, Karolina; Hengstler, Jan G; La Fleur, Linnea; Ekman, Simon; Koyi, Hirsh; Branden, Eva; Ståhle, Elisabeth; Jirström, Karin; Tracy, Derek K; Pontén, Fredrik; Botling, Johan; Rahnenführer, Jörg; Micke, Patrick

    2017-03-10

    Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes. The five selected proteins (MKI67, EZH2, SLC2A1, CADM1, and NKX2-1 alias TTF1) were analyzed by immunohistochemistry on tissue microarrays including tissue from 326 non-small cell lung cancer patients. One score was obtained for each tumor and each protein. The scores were combined, with or without the inclusion of clinical parameters, and the best prognostic model was defined according to the corresponding concordance index (C-index). The best-performing model was subsequently validated in an independent cohort consisting of tissue from 345 non-small cell lung cancer patients. The model based only on protein expression did not perform better compared to clinicopathological parameters, whereas combining protein expression with clinicopathological data resulted in a slightly better prognostic performance (C-index: all non-small cell lung cancer 0.63 vs 0.64; adenocarcinoma: 0.66 vs 0.70, squamous cell carcinoma: 0.57 vs 0.56). However, this modest effect did not translate into a significantly improved accuracy of survival prediction. The combination of a prognostic biomarker panel with clinicopathological parameters did not improve survival prediction in non-small cell lung cancer, questioning the potential of immunohistochemistry-based assessment of protein biomarkers for prognostication in clinical practice.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.14.

  8. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Huang, Hsiang-Wei; Chi, Hsiang-Cheng; Lin, Yang-Hsiang; Lu, Pei-Hsuan; Lin, Kwang-Huei

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. PMID:27322246

  9. Serum APN/CD13 as a novel diagnostic and prognostic biomarker of pancreatic cancer

    PubMed Central

    Xia, Yan; Wang, Dawei; Wang, Guoqing; Meng, Xiangwei

    2016-01-01

    Aminopeptidase N, also known as CD13, has been reported to be overexpressed in several cancers and may contribute to tumor metastasis and angiogenesis. The aim of this study was to evaluate whether serum APN/CD13 could be a potential biomarker for the diagnosis and prognosis of pancreatic cancer (PC). Serum APN/CD13 and carbohydrate antigen 19-9 (CA19-9) levels were measured from 382 participants, which comprised of 204 participants with PC, 48 participants with benign pancreatic tumors (BPT), 43 participants with chronic pancreatitis (CP) and 87 healthy controls (HC). We used receiver operating characteristic (ROC) analysis to calculate diagnostic accuracy. The association of serum APN/CD13 levels with the clinicopathological characteristics of PC patients and their survival was investigated. Serum APN/CD13 levels were substantially higher in PC patients than in controls. ROC analysis revealed that APN/CD13 was significantly better than CA19-9 in differentiating patients with PC from controls. Similar results were noted for early-stage PC. Moreover, the combined use of APN/CD13 and CA19-9 data improved the diagnostic accuracy for PC vs. controls, compared with either test alone. High serum APN/CD13 levels were associated with tumor size, lymph nodes, and metastasis (TNM) stage. Multivariate and ROC curve analyses revealed that high serum APN/CD13 level is an independent factor for predicting mortality and overall survival (OS). Moreover, Kaplan–Meier analysis demonstrated an inverse correlation between increased serum APN/CD13 level and OS. Our study established that serum APN/CD13 may be a novel diagnostic and prognostic biomarker for PC. PMID:27788483

  10. Prognostic significance of tumor subtypes in male breast cancer: a population-based study.

    PubMed

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Vallejo, Carlos Teodoro; Leone, Bernardo Amadeo

    2015-08-01

    Substantial controversy exists about the prognostic role of tumor subtypes in male breast cancer (MaBC). The aim of this study was to analyze the characteristics of each tumor subtype in MaBC and its association with prognosis compared with other factors. We evaluated MaBC patients between 2010 and 2012 with known estrogen receptor, progesterone receptor [together hormone receptor (HR)] status, and human epidermal growth factor receptor 2 (HER2) status reported to the Surveillance, Epidemiology, and End Results program. Patients were classified as: HR-positive/HER2-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). Univariate and multivariate analyses determined the effect of each variable on overall survival (OS). We included 960 patients. Patient distribution was 84.9 % HR-positive/HER2-negative, 11.6 % HR-positive/HER2-positive, 0.6 % HR-negative/HER2-positive, and 2.9 % TN. TN patients were younger, had higher grade, presented with more advanced stage, were more likely to have mastectomy, and to die of breast cancer (all P < 0.05). Univariate analysis showed that HER2 positivity was associated with shorter OS (hazard ratio 1.90, P = 0.031) and TN patients had worse prognosis (hazard ratio 5.10, P = 0.0004). In multivariate analysis, older patients (hazard ratio 3.10, P = 0.032), those with stage IV (hazard ratio 16.27, P < 0.001) and those with TN tumors (hazard ratio 4.61, P = 0.002) had significantly worse OS. We observed significant differences in patient characteristics according to tumor subtype. HER2-positive and TN represented a small proportion of cases. In addition to age and stage, tumor subtype has clear influence on OS in MaBC.

  11. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

    SciTech Connect

    Schwarz, Julie K.; Lewis, James S.; Pfeifer, John; Huettner, Phyllis; Grigsby, Perry

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  12. Prognostic value of pre-therapy platelet elevation in oropharyngeal cancer patients treated with chemoradiation

    PubMed Central

    Shoultz-Henley, Sara; Garden, Adam S.; Mohamed, Abdallah S. R.; Sheu, Tommy; Kroll, Michael H.; Rosenthal, David I.; Gunn, G. Brandon; Hayes, Amos J.; French, Chloe; Eichelberger, Hillary; Kalpathy-Cramer, Jayashree; Smith, Blaine D.; Phan, Jack; Ayoub, Zeina; Lai, Stephen Y.; Pham, Brian; Kies, Merrill; Gold, Kathryn A.; Sturgis, Erich; Fuller, Clifton D.

    2016-01-01

    The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. 433 oropharyngeal cancer patients (OPC) treated with intensity modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data was extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (p<0.03, p<0.04, and p<0.0001, respectively) for patients with PLT pre-chemoRT value of ≥350 × 109/L. Actuarial 5-year locoregional control (LRC) and FDM were 83% and 85% for non-thrombcythemic patients while patient with high platelets had 5-year LRC and FDM of 73% and 74%, respectively. Likew