Science.gov

Sample records for cancer prognosis programme

  1. The West Midlands Bladder Cancer Prognosis Programme: rationale and design.

    PubMed

    Zeegers, Maurice P; Bryan, Richard T; Langford, Carolyn; Billingham, Lucinda; Murray, Paul; Deshmukh, Neeta S; Hussain, Syed; James, Nick; Wallace, D Michael A; Cheng, K K

    2010-03-01

    OBJECTIVE To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design. METHODS There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showed that lifestyle factors are important for determining the risk of bladder cancer, but little is known about their importance in determining the risk of recurrence or progression after diagnosis. Also, histopathological factors alone provide only crude prognostication; the analysis of molecular markers represents a method for refinement but research in this area has not been useful in informing therapeutic decisions or prognostication. The BCPP is a prospective longitudinal cohort study of all patients with newly diagnosed bladder cancer within the West Midlands (UK), investigating the influence of lifestyle factors on recurrence and progression, health-related quality of life, the predictive effect of a panel of molecular markers on recurrence or progression, and the establishment of Europe's largest comprehensive bladder cancer bio-repository. It also incorporates the first randomized clinical trial on the efficacy of selenium and vitamin E on bladder cancer. The numbers and proportions of eligible patients recruited, questionnaires completed and specimens obtained were all recorded. RESULTS Since December 2005, 771 patients have been recruited (68% of eligible patients) and of these, 331 are currently being followed up by questionnaires. We have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients, respectively. CONCLUSIONS The design of the BCPP has allowed this study to be incorporated into routine clinical work throughout the West Midlands, achieving high levels of recruitment, and data and specimen collection. This might represent a model for the future investigation of urological and other malignancies.

  2. Prognosis - Cancer Currents Blog

    Cancer.gov

    A catalog of posts from NCI’s Cancer Currents blog on research related to cancer prognosis. Includes posts on factors that influence prognosis, prognostic biomarkers, and doctor-patient communications about prognosis.

  3. Understanding Your Cancer Prognosis

    Cancer.gov

    Understanding Your Cancer Prognosis is the main video in the NCI Prognosis Video Series, which offers the perspectives of three cancer patients and their doctor, an oncologist who is also a national expert in doctor-patient communication.

  4. Understanding Cancer Prognosis

    MedlinePlus Videos and Cool Tools

    ... A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research ... Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

  5. LRIG and cancer prognosis.

    PubMed

    Lindquist, David; Kvarnbrink, Samuel; Henriksson, Roger; Hedman, Håkan

    2014-09-01

    Optimal treatment decisions for cancer patients require reliable prognostic and predictive information. However, this information is inadequate in many cases. Several recent studies suggest that the leucine-rich repeats and immunoglobulin-like domains (LRIG) genes, transcripts, and proteins have prognostic implications in various cancer types. Relevant literature was identified on PubMed using the key words lrig1, lrig2, and lrig3. LRIG mRNA expression in cancer versus normal tissues was investigated using the Oncomine database. The three human LRIG genes, LRIG1, LRIG2, and LRIG3, encode single-pass transmembrane proteins. LRIG1 is a negative regulator of growth factor signaling that has been shown to function as a tumor suppressor in vitro and in vivo in mice. The functions of LRIG2 and LRIG3 are less well defined. LRIG gene and protein expression are commonly dysregulated in human cancer. In early stage breast cancer, LRIG1 copy number was recently shown to predict early and late relapse in addition to overall survival; in nasopharyngeal carcinoma, loss of LRIG1 is also associated with poor survival. LRIG gene and protein expression have prognostic value in breast cancer, uterine cervical cancer, head-and-neck cancer, glioma, non-small cell lung cancer, prostate cancer, and cutaneous squamous cell carcinoma. In general, expression of LRIG1 and LRIG3 is associated with good survival, whereas expression of LRIG2 is associated with poor survival. Additionally, LRIG1 regulates cellular sensitivity to anti-cancer drugs, which indicates a possible role as a predictive marker. LRIG gene statuses and mRNA and protein expression are clinically relevant prognostic indicators in several types of human cancer. We propose that LRIG analyses could become important when making informed and individualized clinical decisions regarding the management of cancer patients.

  6. Prognosis of Lung Cancer: Heredity or Environment

    DTIC Science & Technology

    2015-06-01

    AWARD NUMBER: W81XWH-12-1-0547 TITLE: Prognosis of Lung Cancer: Heredity or Environment? PRINCIPAL INVESTIGATOR: Melinda Aldrich...0547 Prognosis of Lung Cancer: Heredity or Environment? 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Aldrich...DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Lung cancer is the

  7. Venous Thromboembolism and Prognosis in Cancer

    PubMed Central

    Khorana, Alok A.

    2010-01-01

    Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. PMID:20097409

  8. Adaptive immunity programmes in breast cancer.

    PubMed

    Varn, Frederick S; Mullins, David W; Arias-Pulido, Hugo; Fiering, Steven; Cheng, Chao

    2017-01-01

    The role of the immune system in shaping cancer development and patient prognosis has recently become an area of intense focus in industry and academia. Harnessing the adaptive arm of the immune system for tumour eradication has shown great promise in a variety of tumour types. Differences between tissues, however, necessitate a greater understanding of the adaptive immunity programmes that are active within each tumour type. In breast cancer, adaptive immune programmes play diverse roles depending on the cellular infiltration found in each tumour. Cytotoxic T lymphocytes and T helper type 1 cells can induce tumour eradication, whereas regulatory T cells and T helper type 2 cells are known to be involved in tumour-promoting immunosuppressive responses. Complicating these matters, heterogeneous expression of hormone receptors and growth factors in different tumours leads to disparate, patient-specific adaptive immune responses. Despite this non-conformity in adaptive immune behaviours, encouraging basic and clinical results have been observed that suggest a role for immunotherapeutic approaches in breast cancer. Here, we review the literature pertaining to the adaptive immune response in breast cancer, summarize the primary findings relating to the breast tumour's biology, and discuss potential clinical immunotherapies. © 2016 John Wiley & Sons Ltd.

  9. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms.

  10. Seasonal variations of cancer incidence and prognosis.

    PubMed

    Moan, Johan; Lagunova, Zoya; Bruland, Oyvind; Juzeniene, Asta

    2010-04-01

    The overall death rates are highest in the winter season in many countries at high latitudes. In some but not all countries, this is also true for more specific diseases such as cancer, cardiovascular diseases and influenza. For internal cancers we find no consistent, significant seasonal variation, neither of incidence nor of death rates. On the other hand, we find a significant seasonal variation of cancer prognosis with season of diagnosis in Norway. Best prognosis is found for summer and autumn diagnosis; i.e., for the seasons of the best status of vitamin D in the population. There were no corresponding seasonal variations, neither of the rates of diagnosis, nor of the rates of death which could explain the variations of prognosis. The most likely reason for this variation is that the vitamin D status in Norway is significantly better in summer and autumn than in winter and spring. Earlier, seasonal variations have been explained by circannual variations of certain hormones, but the data are not consistent.

  11. Seasonal variations of cancer incidence and prognosis

    PubMed Central

    Moan, Johan; Bruland, Øyvind; Juzeniene, Asta

    2010-01-01

    The overall death rates are highest in the winter season in many countries at high latitudes. In some but not all countries, this is also true for more specific diseases such as cancer, cardiovascular diseases and influenza. For internal cancers we find no consistent, significant seasonal variation, neither of incidence nor of death rates. On the other hand, we find a significant seasonal variation of cancer prognosis with season of diagnosis in Norway. Best prognosis is found for summer and autumn diagnosis; i.e., for the seasons of the best status of vitamin D in the population. There were no corresponding seasonal variations, neither of the rates of diagnosis, nor of the rates of death which could explain the variations of prognosis. The most likely reason for this variation is that the vitamin D status in Norway is significantly better in summer and autumn than in winter and spring. Earlier, seasonal variations have been explained by circannual variations of certain hormones, but the data are not consistent. PMID:21547098

  12. [Circulating tumor cells and prostate cancer prognosis].

    PubMed

    Capoun, Otakar; Soukup, Viktor; Mikulová, Veronika; Jančíková, Markéta; Honová, Hana; Kološtová, Katarína; Zima, Tomáš; Hanuš, Tomáš

    2014-01-01

    Prostate cancer (PC) is the most common malignant disease in men. Prognosis of patients with metastatic PC is generally unfavourable; however there are significant differences in survival at this stage of the disease. The definition of prognosis is essential for the selection of therapy, respecting an individual risk. In recent years, the association between circulating tumor cells (CTC) detection and response to PC treatment has been widely investigated. Detection of CTC is based on a metastatic process theory and uses well-known tumor-specific antigens on the cell surface. Individual methods assess CTC with different sensitivity and are not yet efficient at the localised PC stage. Only the method of immunomagnetic separation and semi-automatic visualisation (CellSearchTM) has been validated and approved for the use in the PC management. Assessment of the CTC count directly correlates with the prognosis of patients with castration-resistant PC. Change in the CTC count during the therapy also considerably improves risk estimation and represents a marker of overall survival. New methods of CTC cultivation and gene profiling may contribute to individualisation of the treatment similarly to breast cancer. The authors present a review article about theory, methods of detection and clinical use of CTC in castration-resistant PC.

  13. Tumor Volumes and Prognosis in Laryngeal Cancer

    PubMed Central

    Issa, Mohamad R.; Samuels, Stuart E.; Bellile, Emily; Shalabi, Firas L.; Eisbruch, Avraham; Wolf, Gregory

    2015-01-01

    Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance. PMID:26569309

  14. Dietary flavonoids, lignans and colorectal cancer prognosis

    PubMed Central

    Zamora-Ros, Raul; Guinó, Elisabeth; Henar Alonso, M.; Vidal, Carmen; Barenys, Mercè; Soriano, Antonio; Moreno, Victor

    2015-01-01

    Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64–2.02; P-trend 0.67) nor with overall survival (HRT3vsT1 1.06, 95% CI 0.69–1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis. PMID:26369380

  15. Prolonged Nightly Fasting and Breast Cancer Prognosis.

    PubMed

    Marinac, Catherine R; Nelson, Sandahl H; Breen, Caitlin I; Hartman, Sheri J; Natarajan, Loki; Pierce, John P; Flatt, Shirley W; Sears, Dorothy D; Patterson, Ruth E

    2016-08-01

    Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes. To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep. Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015. Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4. Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein. The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95

  16. [Treatment and prognosis of oral cancer].

    PubMed

    de Visscher, J G A M

    2008-04-01

    Squamous cell carcinoma is the most common variety of malignant oral tumour. Most commonly oral carcinomas occur at the lateral tongue surfaces and at the anterior part of the floor of the mouth. If oral cancer is suspected, a dentist will refer the patient to an oral and maxillofacial surgeon who will perform a biopsy. When the diagnosis squamous cell carcinoma is established, the patient will be referred to a multidisciplinary head and neck oncological centre for additional diagnostics and treatment. Depending upon size, location and extent of the tumour and the presence or absence of regional metastases, the management may include surgical excision, radiotherapy or a combination of surgery and radiotherapy. The prognosis is mainly determined by the size of the tumour and regional lymph node involvement. Therefore, early detection is of utmost importance.

  17. Novel predictive biomarkers for cervical cancer prognosis

    PubMed Central

    Moreno-Acosta, Pablo; Carrillo, Schyrly; Gamboa, Oscar; Romero-Rojas, Alfredo; Acosta, Jinneth; Molano, Monica; Balart-Serra, Joseph; Cotes, Martha; Rancoule, Chloé; Magné, Nicolas

    2016-01-01

    High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets. PMID:28101358

  18. MicroRNAs in Testicular Cancer Diagnosis and Prognosis.

    PubMed

    Ling, Hui; Krassnig, Lisa; Bullock, Marc D; Pichler, Martin

    2016-02-01

    Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity. In this review, we present literature findings on miRNAs associated with testicular cancer, and discuss their potential diagnostic and prognostic values, as well as their potential as indicators of drug response in patients with testicular cancer.

  19. [Breast cancer prognosis in Salah Azaiez Institute of Cancer, Tunis].

    PubMed

    Ben Gobrane, H; Fakhfakh, R; Rahal, K; Ben Ayed, F; Mâalej, M; Ben Abdallah, M; Achour, N; Hsairi, M

    2007-01-01

    We estimated survival rate at 9 years of all (470) women with breast cancer diagnosed at Salah Azaïez Institute of Cancer in Tunis to identify the main prognosis factors. Data were collected on residence, socioeconomic level, circumstances of discovery of the tumour, histological type, tumour size, presence of metastases, extension of the tumour, treatment and survival. Comparison of survival curves was done with Log Rank test. Cox model was used for multivariate adjustments and calculation of the hazard ratio (HR) (relative risk of death). There was a survival rate of 61% at 5 years and of 51% at 9 years. Tumour size >5 cm was significantly associated with lower survival as was capsular rupture. After stratification for tumour size and age, only surgery and radiotherapy were significantly associated with improved survival.

  20. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    PubMed Central

    Torres, Carolina; Linares, Ana; Alejandre, Maria José; Palomino-Morales, Rogelio J.; Caba, Octavio; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.; Rojas, Ignacio; Perales, Sonia

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  1. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

    PubMed

    Torres, Carolina; Linares, Ana; Alejandre, Maria José; Palomino-Morales, Rogelio J; Caba, Octavio; Prados, Jose; Aránega, Antonia; Delgado, Juan R; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M; Rojas, Ignacio; Perales, Sonia

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  2. Recent perspectives of breast cancer prognosis and predictive factors

    PubMed Central

    Cao, Su-Sheng; Lu, Cun-Tao

    2016-01-01

    Breast cancer is the most common type of cancer affecting women worldwide. Although there have been great improvements in treating the disease and at present between 80 and 90% of the women survive ≥5-years after their primary diagnosis. However, due to the high incidence of the disease >450,000 women succumb to breast cancer annually worldwide. The majority of improvements in breast cancer survival may be explained through better knowledge of the development and progression of the disease. Consequently, the treatments employed have become more effective. Furthermore, continuous efforts are being made for the identification of novel and efficient biomarkers for the timely prognosis of breast cancer. The present review aims to examine recent perspectives of breast cancer prognosis and the predictive factors involved. PMID:27900052

  3. BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.

    PubMed

    Ursaru, Manuela; Jari, Irma; Gheorghe, Liliana; Naum, A G; Scripcariu, V; Negru, D

    2016-01-01

    To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer. 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis. Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death. Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.

  4. Diabetes mellitus and prognosis in women with breast cancer

    PubMed Central

    Zhao, Xiao-Bo; Ren, Guo-Sheng

    2016-01-01

    Abstract Background: Diabetes mellitus is associated with an increased risk of breast cancer, but studies of the effects of diabetes on the prognosis of women with breast cancer have yielded inconsistent findings. The present meta-analysis aimed to investigate the impact of preexisting diabetes on the prognosis in terms of overall survival (OS), disease-free survival (DFS), and relapse-free period (RFP) in women with breast cancer. Methods: We searched the Embase and PubMed databases until June 2016 for cohort or case–control studies assessing the impact of diabetes on the prognosis of women with breast cancer. The pooled multivariate adjusted hazard ratio (HR) and their 95% confidence intervals (CIs) for OS, DFS, and RFP were used to analyze the impact of diabetes on the prognosis of breast cancer patients. Results: Seventeen studies involving 48,315 women with breast cancer met our predefined inclusion criteria. Meta-analysis showed that the pooled adjusted HR was 1.51 (95% CI 1.34–1.70) for OS and 1.28 (95% CI 1.09–1.50) for DFS in breast cancer patients with diabetes compared to those without diabetes. However, RFP did not differ significantly between patients with and without diabetes (HR 1.42; 95% CI 0.90–2.23). Conclusions: The present meta-analysis suggests that preexisting diabetes is independently associated with poor OS and DFS in female breast cancer patients. However, the impact of diabetes on RFP should be further verified. More prospective studies are warranted to investigate whether appropriate glycemic control with modification of antihyperglycemic agents can improve the prognosis of female breast cancer patients with diabetes. PMID:27930583

  5. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2014-12-01

    pathologists. In the end, the pathologists have resorted to scoring the slides either by directly reading the images scanned from the Leica scanner...stains. Regardless, the reading of 5304 cores requires a single pathologist on average approximately 70 hours to look at and score all of the cores...addition, we have proposed testing a series of biomarkers of prognosis and a set of biomarkers that correlate with Gleason Score . We have made

  6. Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

    PubMed Central

    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-01-01

    Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

  7. A genetic programming approach to oral cancer prognosis

    PubMed Central

    Tan, Mei Sze; Tan, Jing Wei; Yap, Hwa Jen; Abdul Kareem, Sameem; Zain, Rosnah Binti

    2016-01-01

    Background The potential of genetic programming (GP) on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis. Method GP is applied on an oral cancer dataset that contains 31 cases collected from the Malaysia Oral Cancer Database and Tissue Bank System (MOCDTBS). The feature subsets that is automatically selected through GP were noted and the influences of this subset on the results of GP were recorded. In addition, a comparison between the GP performance and that of the Support Vector Machine (SVM) and logistic regression (LR) are also done in order to verify the predictive capabilities of the GP. Result The result shows that GP performed the best (average accuracy of 83.87% and average AUROC of 0.8341) when the features selected are smoking, drinking, chewing, histological differentiation of SCC, and oncogene p63. In addition, based on the comparison results, we found that the GP outperformed the SVM and LR in oral cancer prognosis. Discussion Some of the features in the dataset are found to be statistically co-related. This is because the accuracy of the GP prediction drops when one of the feature in the best feature subset is excluded. Thus, GP provides an automatic feature selection function, which chooses features that are highly correlated to the prognosis of oral cancer. This makes GP an ideal prediction model for cancer clinical and genomic data that can be used to aid physicians in their decision making stage of diagnosis or prognosis. PMID:27688975

  8. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2014-10-01

    Ziding Feng, Ph.D. CONTRACTING ORGANIZATION: The University of Texas MD Anderson Cancer Center Houston, TX 77030-4009 REPORT DATE: October 2014 TYPE...7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER The University of Texas MD Anderson Cancer Center 1515...are underway. I requested and received an extension of my half of the award because of my move from Seattle to MD Anderson Cancer Center in Houston

  9. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    PubMed

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  10. Breast cancer control programme in developing countries.

    PubMed

    Pinotti, J A; Barros, A C; Hegg, R; Zeferino, L C

    1993-01-01

    Breast cancer is a very important health problem in developing countries, where its incidence has increased in the last decades. Mortality rates due to breast cancer have also increased, and the main reason for this is late diagnosis. The authors demonstrate that organizing programmes for early breast cancer detection is possible by making use of simple resources. A set of tiered interventions is proposed, stratified in levels of complexity: Level 1--Identification of abnormal breast by health professionals; Level 2--Medical assistance to women whose breast is considered abnormal, in order to diagnose and treat benign diseases and recognize suspect cases of cancer; Level 3--Management of the women with suspected or diagnosed breast cancer by a multidisciplinary team. Therefore, a proposal for wide action for breast cancer control in developing countries is presented.

  11. Data Requirements for Model-Based Cancer Prognosis Prediction

    PubMed Central

    Dalton, Lori A.; Yousefi, Mohammadmahdi R.

    2015-01-01

    Cancer prognosis prediction is typically carried out without integrating scientific knowledge available on genomic pathways, the effect of drugs on cell dynamics, or modeling mutations in the population. Recent work addresses some of these problems by formulating an uncertainty class of Boolean regulatory models for abnormal gene regulation, assigning prognosis scores to each network based on intervention outcomes, and partitioning networks in the uncertainty class into prognosis classes based on these scores. For a new patient, the probability distribution of the prognosis class was evaluated using optimal Bayesian classification, given patient data. It was assumed that (1) disease is the result of several mutations of a known healthy network and that these mutations and their probability distribution in the population are known and (2) only a single snapshot of the patient’s gene activity profile is observed. It was shown that, even in ideal settings where cancer in the population and the effect of a drug are fully modeled, a single static measurement is typically not sufficient. Here, we study what measurements are sufficient to predict prognosis. In particular, we relax assumption (1) by addressing how population data may be used to estimate network probabilities, and extend assumption (2) to include static and time-series measurements of both population and patient data. Furthermore, we extend the prediction of prognosis classes to optimal Bayesian regression of prognosis metrics. Even when time-series data is preferable to infer a stochastic dynamical network, we show that static data can be superior for prognosis prediction when constrained to small samples. Furthermore, although population data is helpful, performance is not sensitive to inaccuracies in the estimated network probabilities. PMID:27127404

  12. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  13. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  14. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  15. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  16. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  17. Breast cancer prognosis predicted by nuclear receptor-coregulator networks.

    PubMed

    Doan, Tram B; Eriksson, Natalie A; Graham, Dinny; Funder, John W; Simpson, Evan R; Kuczek, Elizabeth S; Clyne, Colin; Leedman, Peter J; Tilley, Wayne D; Fuller, Peter J; Muscat, George E O; Clarke, Christine L

    2014-07-01

    Although molecular signatures based on transcript expression in breast cancer samples have provided new insights into breast cancer classification and prognosis, there are acknowledged limitations in current signatures. To provide rational, pathway-based signatures of disrupted physiology in cancer tissues that may be relevant to prognosis, this study has directly quantitated changed gene expression, between normal breast and cancer tissue, as a basis for signature development. The nuclear receptor (NR) family of transcription factors, and their coregulators, are fundamental regulators of every aspect of metazoan life, and were rigorously quantified in normal breast tissues and ERα positive and ERα negative breast cancers. Coregulator expression was highly correlated with that of selected NR in normal breast, particularly from postmenopausal women. These associations were markedly decreased in breast cancer, and the expression of the majority of coregulators was down-regulated in cancer tissues compared with normal. While in cancer the loss of NR-coregulator associations observed in normal breast was common, a small number of NR (Rev-ERBβ, GR, NOR1, LRH-1 and PGR) acquired new associations with coregulators in cancer tissues. Elevated expression of these NR in cancers was associated with poorer outcome in large clinical cohorts, as well as suggesting the activation of ERα -related, but ERα-independent, pathways in ERα negative cancers. In addition, the combined expression of small numbers of NR and coregulators in breast cancer was identified as a signature predicting outcome in ERα negative breast cancer patients, not linked to proliferation and with predictive power superior to existing signatures containing many more genes. These findings highlight the power of predictive signatures derived from the quantitative determination of altered gene expression between normal breast and breast cancers. Taken together, the findings of this study identify networks

  18. High Hepsin expression predicts poor prognosis in Gastric Cancer

    PubMed Central

    Zhang, Mingming; Zhao, Junjie; Tang, Wenyi; Wang, Yanru; Peng, Peike; Li, Lili; Song, Shushu; Wu, Hao; Li, Can; Yang, Caiting; Wang, Xuefei; Zhang, Chunyi; Gu, Jianxin

    2016-01-01

    Hepsin, a membrane-associated serine protease, is frequently upregulated in epithelial cancers and involved in cancer progression. Our study aims to describe the expression pattern and evaluate the clinical implication of hepsin in gastric cancer patients. The mRNA expression of hepsin was analyzed in 50 gastric cancer and matched non-tumor tissues, which was downregulated in 78% (39/50) of gastric cancer. By searching and analyzing four independent datasets from Oncomine, we obtained the similar results. Furthermore, we evaluated the hepsin expression by IHC in tissue microarray (TMA) containing 220 Gastric Cancer specimens. More importantly, Kaplan-Meier survival and Cox regression analyses were taken to access the prognosis of gastric cancer and predicted that hepsin protein expression was one of the significant and independent prognostic factors for overall survival of Gastric Cancer. PMID:27841306

  19. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2013-10-01

    incontinence and urinary urgency as well as sexual dysfunction. Furthermore, evidence from many sources suggests that most prostate cancers are...mainly surgery and radiation therapy, result in well documented significant morbidities, including significant lower urinary tract symptoms such as

  20. Histone modifications in cancer biology and prognosis.

    PubMed

    Kurdistani, Siavash K

    2011-01-01

    Cancer is a disease of genome sequence alterations as well as epigenetic changes. Epigenetics refers in part to the mechanisms by which histones affect various DNA-based processes, such as gene regulation. Histones are proteins around which the DNA wraps itself to form chromatin--the physiologically relevant form of the human genome. Histones are modified extensively by posttranslational modifications that alter chromatin structure and serve to recruit to or exclude protein complexes from DNA. Aberrations in histone modifications occur frequently in cancer including changes in their levels and distribution at gene promoters, gene coding regions, repetitive DNA sequences, and other genomic elements. Locus-specific alterations in histone modifications may have adverse effects on expression of nearby genes but so far have not been shown to have clinical utility. Cancer cells also exhibit alterations in global levels of specific histone modifications, generating an additional layer of epigenetic heterogeneity at the cellular level in tumor tissues. Unlike locus-specific changes, the cellular epigenetic heterogeneity can be used to define previously unrecognized subsets of cancer patients with distinct clinical outcomes. In general, increased prevalence of cells with lower global levels of histone modifications is prognostic of poorer clinical outcome such as increased risk of tumor recurrence and/or decreased survival probability. Prognostic utility of histone modifications has been demonstrated independently for multiple cancers including those of prostate, lung, kidney, breast, ovary, and pancreas, suggesting a fundamental association between global histone modification levels and tumor aggressiveness, regardless of cancer tissue of origin. Cellular levels of histone modifications may also predict response to certain chemotherapeutic agents, serving as predictive biomarkers that could inform clinical decisions on choice and course of therapy. The challenge before us

  1. Immune cell interplay in colorectal cancer prognosis.

    PubMed

    Norton, Samuel E; Ward-Hartstonge, Kirsten A; Taylor, Edward S; Kemp, Roslyn A

    2015-10-15

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  2. Is obesity an independent prognosis factor in woman breast cancer?

    PubMed

    Majed, Bilal; Moreau, Thierry; Senouci, Kamel; Salmon, Rémi J; Fourquet, Alain; Asselain, Bernard

    2008-09-01

    Breast cancer and obesity represent important public health issues in most western countries. A number of studies found a negative prognosis effect of obesity or excess of weight in woman breast cancer. However, to date, this issue remains controversial. The objectives of this study were to confirm the prognosis role of obesity on a large cohort of patients and to investigate a potential independent effect. We constituted a cohort of 14,709 patients who were recruited and treated at the Curie Institute (Paris) from 1981 to 1999. These patients were followed prospectively for a first unilateral invasive breast cancer without distant metastasis. Obesity was defined by a Body Mass Index (BMI) above 30 kg/m(2) according to the World Health Organization recommendations. Obese patients (8%) presented more extended tumors at diagnosis time suggesting a delayed breast cancer diagnosis. However, obesity appeared as a negative prognosis factor for several events in respectively univariate and multivariate survival analysis: metastasis recurrence (HR = 1.32[1.19-1.48]; HR = 1.12[1.00-1.26]), disease free interval (1.20[1.08-1.32]; 1.10[0.99-1.22]), overall survival (1.43[1.28-1.60]; 1.12[0.99-1.25]) and second primary cancer outcome (1.57[1.19-2.07]; 1.43[1.09-1.89]). Even if obese patients presented more advanced tumors at diagnosis time, multivariate analysis showed that there was a relevant independent effect. Other BMI codings, distinguishing overweight patients or using BMI as a continuous variable, showed a consistent correlation between BMI's value and prognosis effect. Interaction analysis revealed a more important obesity effect in the presence of tumor estrogen receptors and among limited extent tumors. This survey confirms the prognosis role of obesity on one of the largest cohort by investigating several prognosis events. While independent obesity effect linked to hormonal disorders appeared consistent as obesity's mechanism, we stress that obesity prognosis

  3. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2016-11-01

    misclassified and actually have occult high-risk features or are destined to progress to high-risk disease. Therefore a critical need in localized...prostate cancer is the development of biomarkers that predict occult or incipient aggressive disease in the low-risk population. To address this

  4. Autoimmune Thyroid Disease and Breast Cancer Prognosis

    PubMed Central

    Özmen, Tolga; Güllüoğlu, Bahadır Mahmut; Yegen, Cumhur Şevket; Soran, Atilla

    2015-01-01

    Objective The association of breast cancer and thyroid autoimmunity has been suggested by many studies in the literature, but the causality still needed to be proven. With this study we aimed to search the correlation between thyroid autoimmunity and breast cancer prognostic factors. Materials and Methods To this prospective cohort study 200 consecutive breast cancer patients, who were operated in our clinic were included. Patients’ serum thyroid hormone, anti-thyroglobuline (anti-TG) and anti-thyroid peroxidase (anti-TPO) levels and tumors’ prognostic parameters (tumor size, axillary involvement, histological grade, lymphovascular invasion, receptor status, Ki-67 proliferation index) were collected. The correlation between serum thyroid autoantibody levels and tumor’s prognostic factors were studied. Results The prevalence of thyroid autoimmunity (high levels of serum anti-TPO and/or anti-TG) was 18.5% (n=37). Patients with thyroid autoimmunity had a significant lower rate of axillary involvement and a lower rate of Ki-67 proliferation index (22% vs. 46% [p=0,007] and 12.73% vs. 20.72% [p=0.025], respectively) and were more commonly included to the “low-risk” group (<14%) according to their Ki-67 scores (68% vs. 46%; p=0.015). Other parameters did not differ between the two groups. Conclusion We found a favorable correlation between thyroid autoimmunity and axillary involvement and also Ki-67 proliferation index score, which are two crucial and strongly predictive parameters of breast cancer prognoses. This supports the idea of thyroid autoimmunity being a favorable prognostic parameter. Further studies are necessary to investigate the reasons of protective or predictive effect of high thyroid peroxidase levels in breast cancer patients.

  5. Trends in cancer prognosis in a population-based cohort survey: can recent advances in cancer therapy affect the prognosis?

    PubMed

    Kawabata-Shoda, Eri; Charvat, Hadrien; Ikeda, Ai; Inoue, Manami; Sawada, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Shimazu, Taichi; Yamaji, Taiki; Kimura, Hiromichi; Masuda, Sachiko; Tsugane, Shoichiro

    2015-02-01

    The aim of the study was to investigate trends in cancer prognosis by examining the relationship between period of diagnosis and probability of death from cancer in a population-based cohort. Within a cohort of Japanese men and women aged 40-69 years and free of prior diagnosis of cancer and cardiovascular disease at baseline, data from 4403 patients diagnosed with cancer between 1990 and 2006 and followed up until 2012 were analyzed using survival regression models to assess the presence of an effect of the period of diagnosis (before 1998 versus after 1998) on the risk of dying from cancer. We noted a significant decrease in risk of dying from cancer among individuals diagnosed after 1998 with lung cancer (hazard ratio [HR]=0.676 [0.571-0.800]) or colorectal cancer (HR=0.801 [0.661-0.970]). A decrease in the estimated five-year probability of death from cancer was also noted between the first (before 1998) and the second (after 1998) period of diagnosis for lung and colorectal cancers (e.g., 85.4% vs. 73.3% for lung cancer and 44.6% vs. 37.7% for colorectal cancer, respectively, for stage III in men aged 60 at diagnosis). This study presented the first scientific evidence of improvement in prognosis for lung and colorectal cancer patients in a population-based cohort in Japan. Our results suggest that recent advances in cancer treatment could have influenced cancer survival differently among lung, colorectal and gastric cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

    PubMed Central

    Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

    2015-01-01

    Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

  7. Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients.

    PubMed

    Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

    2015-10-01

    Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

  8. The Effect of Diabetes Mellitus on Lung Cancer Prognosis

    PubMed Central

    Zhu, Linhai; Cao, Hongxin; Zhang, Tiehong; Shen, Hongchang; Dong, Wei; Wang, Liguang; Du, Jiajun

    2016-01-01

    Abstract Previous studies suggested that diabetes mellitus (DM) was associated with risk and mortality of cancer, but studies investigating the correlation between DM and lung cancer prognosis remain controversial. Herein, a meta-analysis was performed to derive a more precise estimate of the prognostic role of DM in lung cancer. Medline and Embase were searched for eligible articles from inception to October 25, 2015. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) was calculated to evaluate the correlation between DM and lung cancer prognosis. Subgroup meta-analysis was performed based on the histology and the treatment methods. A total of 20 cohort studies from 12 articles were included in the meta-analysis. Also, 16 studies investigated the overall survival (OS) and 4 studies investigated the progression-free survival (PFS). DM was significantly associated with the inferior OS of lung cancer with the pooled HR 1.28 (95% CI: 1.10–1.49, P = 0.001). The association was prominent in the nonsmall cell lung cancer (NSCLC) subgroup (HR 1.35, 95%CI: 1.14–1.60, P = 0.002), whereas the association was not significant in the small cell lung cancer (SCLC) subgroup (HR 1.33, 95% CI: 0.87–2.03, P = 0.18). When NSCLC patients were further stratified by treatment methods, DM had more influence on the surgically treated subgroup than the nonsurgically treated subgroup. There was no obvious evidence for publication bias by Begg's and Egger's test. The results of this meta-analysis exhibit an association of DM with inferior prognosis amongst lung cancer patients, especially the surgically treated NSCLC patients. Given the small number of studies included in this meta-analysis, the present conclusion should be consolidated with more high-quality prospective cohort studies or randomized controlled trials. PMID:27124062

  9. Colorectal cancer prognosis twenty years later

    PubMed Central

    Bujanda, Luis; Sarasqueta, Cristina; Hijona, Elisabeth; Hijona, Lander; Cosme, Angel; Gil, Ines; Elorza, Jose Luis; Asensio, Jose I; Larburu, Santiago; Enríquez-Navascués, José M; Jover, Rodrigo; Balaguer, Francesc; Llor, Xavier; Bessa, Xavier; Andreu, Montserrat; Paya, Artemio; Castells, Antoni; Association, Gastrointestinal Oncology Group of the Spanish Gastroenterological

    2010-01-01

    AIM: To evaluate changes in colorectal cancer (CRC) survival over the last 20 years. METHODS: We compared two groups of consecutive CRC patients that were prospectively recruited: Group I included 1990 patients diagnosed between 1980 and 1994. Group II included 871 patients diagnosed in 2001. RESULTS: The average follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II. Overall median survival was significantly longer in Group II than in Group I (73 mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages. Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only 17% of GroupI patients received chemotherapy compared with 50% of Group II patients (P < 0.001). CONCLUSION: Survival in colorectal cancer patients has doubled over the past 20 years. This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality. PMID:20143465

  10. Association of polymorphisms in TGFB1 and prostate cancer prognosis.

    PubMed

    Brand, Timothy C; Bermejo, Carlos; Canby-Hagino, Edith; Troyer, Dean A; Baillargeon, Jacques; Thompson, Ian M; Leach, Robin J; Naylor, Susan L

    2008-02-01

    Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

  11. [Genomic Tests as Predictors of Breast Cancer Patients Prognosis].

    PubMed

    Bielčiková, Z; Petruželka, L

    2016-01-01

    Hormonal dependent breast cancer is a heterogeneous disease from a molecular and clinical perspective. The relapse risk of early breast cancer patients treated with adjuvant hormonal therapy varies. Validated predictive markers concerning adjuvant cytotoxic treatment are still lacking in ER+/ HER2-  breast cancer, which has a good prognosis in general. This can lead to the inefficient chemotherapy indication. Molecular classification of breast cancer reports evidence about the heterogeneity of hormonal dependent breast cancer and its stratification to different groups with different characteristics. Multigene assays work on the molecular level, and their aim is to provide patients risk stratification and therapy efficacy prediction. The position of multigene assays in clinical practice is not stabile yet. Non uniform level of evidence connected to patients prognosis interpretations and difficult comparison of tests are the key problems, which prevent their wide clinical use. The article is a summary of some of the most important multigene assays in breast cancer and their current position in oncology practice.

  12. Cell Surface Markers in Colorectal Cancer Prognosis

    PubMed Central

    Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.

    2011-01-01

    The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979

  13. Cancer and liver cirrhosis: implications on prognosis and management

    PubMed Central

    Pinter, Matthias; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

    2016-01-01

    Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies. PMID:27843598

  14. LINC00978 predicts poor prognosis in breast cancer patients

    PubMed Central

    Deng, Lin-lin; Chi, Ya-yun; Liu, Lei; Huang, Nai-si; Wang, Lin; Wu, Jiong

    2016-01-01

    Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs in the human genome that involves in breast cancer development and progression. Here, we identify a lncRNA, LINC00978, which is upregulated in breast cancer cell lines and tissues compared with corresponding controls. Furthermore, LINC00978 expression is negatively associated with hormone receptor (HR) status in 195 breast cancer patients studied (p = 0.033). Kaplan–Meier survival analysis shows that patients with high LINC00978 expression have poorer disease-free survival (DFS) than those with low LINC00978 expression (p = 0.012), and multivariate analysis identifies LINC00978 as an independent prognostic factor in breast cancer (p = 0.008, hazard ratio [HR] = 2.270, 95% confidence interval [CI] 1.237–4.165). Our study indicates that LINC00978 may be an oncogene in breast cancer, and can serve as a potential biomarker to predict prognosis in breast cancer patients. PMID:27897214

  15. Somatic mutations, acetylator status, and prognosis in colorectal cancer

    PubMed Central

    Hardingham, J; Butler, W; Roder, D; Dobrovic, A; Dymock, R; Sage, R; Roberts-Thomson, I

    1998-01-01

    Background—Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer. 
Aims—To determine whether cancers with somatic mutations are more frequent in fast acetylators and whether mutations or acetylator status influence prognosis after colorectal surgery. 
Patients—One hundred consecutive subjects undergoing elective surgery for colorectal cancer. 
Methods—Acetylator status was determined by polymerase chain reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutations in K-ras (codon 12) and TP53 were determined by PCR analysis using restriction enzyme digestion and single strand conformation polymorphism respectively. Survival from colorectal cancer for up to five years after diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage. 
Results—Mutations in K-ras and TP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53 mutations (p=0.003) but was not significantly related to acetylator status or the presence of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confidence interval 1.5 to 11.6) when compared with that of a TP53 negative reference group. 
Conclusion—The presence of both TP53 and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage. 

 Keywords: colorectal cancer; TP53 and K-ras mutations; acetylator status; prognosis PMID:9659162

  16. Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities.

    PubMed

    Jiralerspong, Sao; Goodwin, Pamela J

    2016-12-10

    Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes. This is most clearly established for estrogen receptor-positive breast cancer, with the relationship in triple-negative and human epidermal growth factor receptor 2-positive subtypes less well established. A range of biologic mechanisms that may underlie this association has been identified. Weight loss and lifestyle interventions, as well as metformin and other obesity-targeted therapies, are promising avenues that require further study. Conclusion Obesity is associated with inferior survival in breast cancer. Understanding the nature and mechanisms of this effect provides an important opportunity for interventions to improve the diagnosis, treatment, and outcomes of obese patients with breast cancer.

  17. High FOXRED1 expression predicted good prognosis of colorectal cancer

    PubMed Central

    Fei, Weiqiang; Liu, Shuiping; Hu, Xiaotong

    2016-01-01

    The human FAD-dependent oxidoreductase domain containing 1 (FOXRED1) protein is reported as an assembly factor which promotes the correct assembly and stability of mitochondrial Complex I (CI). Alterations of mitochondrial CI might cause tumorigenesis and metastasis, but it’s molecular mechanisms remain unclear. In this study, we selected 145 cases of colorectal cancer for immunohistochemistry to explore the role of FOXRED1 played in the tumor progression of colorectal cancer. The relationship between FOXRED1 expression and clinicopathological features of colorectal cancers was evaluated. FOXRED1 mainly localized in the cytoplasm in the colorectal cancer tissues, and had significant association with histopathological grading, depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P<0.05 for each). However, age, gender and tumor location was not found to be associated with FOXRED1 expression. Colorectal cancer patients with higher expression of FOXRED1 had the higher 3 year survival rate (P=0.003). Moreover, FOXRED1 had potentiality to be an independent prognostic factor for survival in colorectal cancer (P=0.04). Low FOXRED1 expression correlated with poor prognosis of colorectal cancer and targeting this molecular will be a potential treatment strategy for colorectal cancer. PMID:27904784

  18. Epidemiology and prognosis of breast cancer in young women

    PubMed Central

    Assi, Hussein A.; Khoury, Katia E.; Dbouk, Haifa; Khalil, Lana E.; Mouhieddine, Tarek H.

    2013-01-01

    Breast cancer is the most common malignancy in women with 6.6% of cases diagnosed in young women below the age of 40. Despite variances in risk factors, Age Standardized Incidence Rates of breast cancer in young women vary little between different countries. Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer. Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 overexpression. This has a significant negative impact on the rate of local recurrence and overall survival. Moreover, younger women often tend to present with breast cancer at a later stage than their older counterparts, which further explains worse outcome. Despite these factors, age per se is still being advocated as an independent role player in the prognosis. This entails more aggressive treatment modalities and the need for closer monitoring and follow-up. PMID:23819024

  19. Epidemiology and prognosis of breast cancer in young women.

    PubMed

    Assi, Hussein A; Khoury, Katia E; Dbouk, Haifa; Khalil, Lana E; Mouhieddine, Tarek H; El Saghir, Nagi S

    2013-06-01

    Breast cancer is the most common malignancy in women with 6.6% of cases diagnosed in young women below the age of 40. Despite variances in risk factors, Age Standardized Incidence Rates of breast cancer in young women vary little between different countries. Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer. Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 overexpression. This has a significant negative impact on the rate of local recurrence and overall survival. Moreover, younger women often tend to present with breast cancer at a later stage than their older counterparts, which further explains worse outcome. Despite these factors, age per se is still being advocated as an independent role player in the prognosis. This entails more aggressive treatment modalities and the need for closer monitoring and follow-up.

  20. Home-based multidimensional survivorship programmes for breast cancer survivors.

    PubMed

    Cheng, Karis Kin Fong; Lim, Yee Ting Ethel; Koh, Zhi Min; Tam, Wilson Wai San

    2017-08-24

    The prognosis and survival rate of women with breast cancer have significantly improved worldwide. Effective home-based multidimensional programmes for breast cancer survivors have gained an ever greater emphasis in survivorship care to maximise women's quality of life for their successful transition to rehabilitation and normal life. It is important to summarise the best available evidence to evaluate the effects of home-based multidimensional survivorship programmes on quality of life in women within 10 years of the completion of surgery or adjuvant cancer therapy for breast cancer, or both. To assess the effects of home-based, multidimensional survivorship (HBMS) programmes on maintaining or improving the quality of life in breast cancer survivors. In April 2016 we searched the Cochrane Breast Cancer Specialised Register, CENTRAL, PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. We also screened reference lists of all identified studies and contacted study authors. Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of HBMS programmes in maintaining or improving quality of life in women with stages 0 to 3 breast cancer who completed primary cancer treatment (surgery or adjuvant cancer therapy, or both) up to 10 years earlier. We considered studies where the interventions included more than one of the following listed components: educational (such as information provision and self-management advice), physical (such as exercise training and resistance training) and psychological (such as counselling and cognitive therapies), to constitute a multidimensional programme. Interventions had to be allowed to be carried out at home. Two authors independently assessed eligible studies for inclusion, and performed quality assessment and extracted relevant data of the included studies. Quality of life was the primary outcome of

  1. Lifestyle and family history influence cancer prognosis in Brazilian individuals.

    PubMed

    Araújo, Raimundo F; Lira, George A; Guedes, Hugo G; Cardoso, Marília A; Cavalcante, Francisco J; Araújo, Ana Lucia M; Ramos, Carlos César O; de Araújo, Aurigena Antunes

    2013-12-01

    The aim of this research was to study prognostic parameters of CRC by analyzing clinical and pathological variables associated with cancer patients at a northeastern Brazilian Hospital. This was a retrospective study evaluating CRC-diagnosed patients across a 10-year period (1995-2005) at Dr. Luiz Antônio Hospital in Natal, RN, Brazil. Data were collected from patients' medical files. A total of 358 patients were included over the 10-year period. The average age at diagnosis was 58.8 years (S.D.=15.26), 48.3% of the patients were males and 51.7% were females. Alcohol consumption significantly increased the chance of dying (p<0.023) from colorectal cancer; this increased risk of death was approximately 71%, compared to 52.2% of the non-alcoholics. In addition, tobacco increased the chance of developing high TNM stage tumors (level III, IV; p<0.001). Another risk factor for increased mortality was a family history for colorectal cancer (p<0.002). Our analysis found that patients with an unhealthy lifestyle and/or family history of colorectal cancer were more likely to develop advanced stage colorectal cancer and to have a poor disease prognosis compared to patients with healthy lifestyle and/or sporadic colorectal cancer. These data suggest that a mass screening program should be implemented in northeastern Brazil in order to better prevent and treat colorectal cancer. Copyright © 2013 Elsevier GmbH. All rights reserved.

  2. Applications of Machine Learning in Cancer Prediction and Prognosis

    PubMed Central

    Cruz, Joseph A.; Wishart, David S.

    2006-01-01

    Machine learning is a branch of artificial intelligence that employs a variety of statistical, probabilistic and optimization techniques that allows computers to “learn” from past examples and to detect hard-to-discern patterns from large, noisy or complex data sets. This capability is particularly well-suited to medical applications, especially those that depend on complex proteomic and genomic measurements. As a result, machine learning is frequently used in cancer diagnosis and detection. More recently machine learning has been applied to cancer prognosis and prediction. This latter approach is particularly interesting as it is part of a growing trend towards personalized, predictive medicine. In assembling this review we conducted a broad survey of the different types of machine learning methods being used, the types of data being integrated and the performance of these methods in cancer prediction and prognosis. A number of trends are noted, including a growing dependence on protein biomarkers and microarray data, a strong bias towards applications in prostate and breast cancer, and a heavy reliance on “older” technologies such artificial neural networks (ANNs) instead of more recently developed or more easily interpretable machine learning methods. A number of published studies also appear to lack an appropriate level of validation or testing. Among the better designed and validated studies it is clear that machine learning methods can be used to substantially (15–25%) improve the accuracy of predicting cancer susceptibility, recurrence and mortality. At a more fundamental level, it is also evident that machine learning is also helping to improve our basic understanding of cancer development and progression. PMID:19458758

  3. Machine learning applications in cancer prognosis and prediction.

    PubMed

    Kourou, Konstantina; Exarchos, Themis P; Exarchos, Konstantinos P; Karamouzis, Michalis V; Fotiadis, Dimitrios I

    2015-01-01

    Cancer has been characterized as a heterogeneous disease consisting of many different subtypes. The early diagnosis and prognosis of a cancer type have become a necessity in cancer research, as it can facilitate the subsequent clinical management of patients. The importance of classifying cancer patients into high or low risk groups has led many research teams, from the biomedical and the bioinformatics field, to study the application of machine learning (ML) methods. Therefore, these techniques have been utilized as an aim to model the progression and treatment of cancerous conditions. In addition, the ability of ML tools to detect key features from complex datasets reveals their importance. A variety of these techniques, including Artificial Neural Networks (ANNs), Bayesian Networks (BNs), Support Vector Machines (SVMs) and Decision Trees (DTs) have been widely applied in cancer research for the development of predictive models, resulting in effective and accurate decision making. Even though it is evident that the use of ML methods can improve our understanding of cancer progression, an appropriate level of validation is needed in order for these methods to be considered in the everyday clinical practice. In this work, we present a review of recent ML approaches employed in the modeling of cancer progression. The predictive models discussed here are based on various supervised ML techniques as well as on different input features and data samples. Given the growing trend on the application of ML methods in cancer research, we present here the most recent publications that employ these techniques as an aim to model cancer risk or patient outcomes.

  4. Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

    PubMed Central

    Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo

    2016-01-01

    Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844

  5. Prognosis and management of invasive well-differentiated thyroid cancer.

    PubMed

    Urken, Mark L

    2010-04-01

    Invasive thyroid cancer is often asymptomatic and can take the surgeon and the patient by surprise. Maintenance of a high level of suspicion in patients who present with symptoms, an abnormal examination, recurrent disease, or documented metastatic disease lead the clinician to obtain appropriate cross-sectional imaging that helps to define the full extent of the disease. Specific guidelines are provided for the management of the various structures in the neck that are at risk for involvement by disease extension outside the gland or extracapsular extension outside a lymph node with involvement by metastatic disease. This article reviews the prognosis, diagnosis, management, and implications of invasive thyroid cancer affecting the various structures of the central and lateral compartments of the neck. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Metaplastic breast cancer: clinicopathological features and its prognosis.

    PubMed

    Lee, Hyewon; Jung, So-Youn; Ro, Jae Yun; Kwon, Youngmee; Sohn, Joo Hyuk; Park, In Hae; Lee, Keun Seok; Lee, Seeyoun; Kim, Seok Won; Kang, Han Sung; Ko, Kyoung Lan; Ro, Jungsil

    2012-05-01

    The prognosis of metaplastic breast cancer (MBC) is reportedly worse than that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants of poor prognosis are not yet known. Patients from two Korean cancer centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of the two disease groups, including clinical parameters, histological features, chemoresponsiveness, disease recurrence and survival estimates, were evaluated. MBC presented with larger tumours, more frequent distant metastasis and higher histological grade compared with TN-IDC (p<0.001). All but nine patients with MBC had triple-negative disease. Disease-free survival and overall survival (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease-free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95% CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast conserving surgery. For OS, MBC type remained a significant prognostic factor (HR 2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given MBC type, risk factors for disease recurrence included the presence of a squamous component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95% CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR 10.77; 95% CI 2.59 to 44.76). MBC had worse survival outcomes compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent recurrence with high initial stage and the unique biology of MBC itself.

  7. [Vital prognosis in advanced cancer patients: a systematic literature review].

    PubMed

    Tavares, Teresa; Gonçalves, Edna

    2013-01-01

    Prognostication is a critical medical task for the adequacy of treatment and management of priorities and expectations of patients and families. In 2005, the European Association of Palliative Care (EAPC) published recommendations on the formulation of vital prognosis in advanced cancer patients. The aim of this study is to analyze the literature subsequent to this review and to update the presented recommendations. Using the same strategy of the EAPC group, we performed a systematic literature search in the electronic databases PubMed and Scopus, which included original studies in adults with advanced cancer, without tumor-directed treatment, with a median survival of less than 90 days. The articles were analyzed and classified according to the level of evidence by two independent reviewers. The 41 articles analyzed allowed to keep grade A recommendations for clinical estimation of survival and Palliative Prognostic score and now also for Palliative Prognostic Index, performance status, dyspnea, lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C-reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as predictors reached grade B. To formulate the vital prognosis and to communicate it properly to the patient and family are core competencies of physicians, particularly of those who deal with end of life patients. The clinical impression combined with scientific evidence allows us to estimate more accurately the survival, allowing prioritizing and managing more appropriately the existing resources.

  8. Interval cancers in a national colorectal cancer screening programme

    PubMed Central

    Stanners, Greig; Lang, Jaroslaw; Brewster, David H; Carey, Francis A; Fraser, Callum G

    2016-01-01

    Background Little is known about interval cancers (ICs) in colorectal cancer (CRC) screening. Objective The purpose of this study was to identify IC characteristics and compare these with screen-detected cancers (SCs) and cancers in non-participants (NPCs) over the same time period. Design This was an observational study done in the first round of the Scottish Bowel Screening Programme. All individuals (772,790), aged 50–74 years, invited to participate between 1 January 2007 and 31 May 2009 were studied by linking their screening records with confirmed CRC records in the Scottish Cancer Registry (SCR). Characteristics of SC, IC and NPC were determined. Results There were 555 SCs, 502 ICs and 922 NPCs. SCs were at an earlier stage than ICs and NPCs (33.9% Dukes’ A as against 18.7% in IC and 11.3% in NPC), screening preferentially detected cancers in males (64.7% as against 52.8% in IC and 59.7% in NPC): this was independent of a different cancer site distribution in males and females. SC in the colon were less advanced than IC, but not in the rectum. Conclusion ICs account for 47.5% of the CRCs in the screened population, indicating approximately 50% screening test sensitivity: guaiac faecal occult blood testing (gFOBT) sensitivity is less for women than for men and gFOBT screening may not be effective for rectal cancer. PMID:27536369

  9. Dietary intervention strategies to modulate prostate cancer risk and prognosis.

    PubMed

    Freedland, Stephen J; Aronson, William J

    2009-05-01

    There is increasing interest in complementary and holistic approaches for cancer prevention and management. We sought to review the latest literature regarding dietary interventions for prostate cancer with a special emphasis on dietary fat and carbohydrate intake for modulating prognosis among men with prostate cancer. Several recent prospective trials have investigated various dietary and lifestyle investigations on malignant prostate tissue biology. These interventions included a very low-fat (12% fat kcals) vegan diet with various supplements and lifestyle changes, a more traditional low-fat diet (25% fat kcals) with flaxseed supplementation, and a low-glycemic index diet. Low-glycemic index and very low-fat vegan diets (with supplements and lifestyle changes) alter tumor biology as assessed by tumor gene expression changes, with a common mechanism perhaps being weight loss whereas no effects were seen with a traditional low-fat diet. In mice, either very low-fat or low-carbohydrate diets significantly slow tumor growth independent of weight loss. Epidemiologic and preclinical data also suggest cholesterol intake and serum cholesterol levels may be linked with the development and progression of prostate cancer. Small clinical trials suggest that tumor biology can be altered by either a vegan low-fat diet or eliminating simple carbohydrates accompanied by weight loss. Larger and longer term studies are needed to determine the clinical relevance of these findings.

  10. Incorporating Network Structure in Integrative Analysis of Cancer Prognosis Data

    PubMed Central

    Liu, Jin; Huang, Jian; Ma, Shuangge

    2014-01-01

    In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly-connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly-connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate to strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance. PMID:23161517

  11. Characteristics and prognosis of synchronous multiple early gastric cancer

    PubMed Central

    Isobe, Taro; Hashimoto, Kousuke; Kizaki, Junya; Murakami, Naotaka; Aoyagi, Keishiro; Koufuji, Kikuo; Akagi, Yoshito; Shirouzu, Kazuo

    2013-01-01

    AIM: To assess the clinicopathologic characteristics, risk factors, and prognosis for synchronous multiple early gastric cancer (SMGC). METHODS: A total of 146 patients with SMGC and 1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival. Tumors were classified into groups on the basis of location and histology. Smoking habits were evaluated using the Brinkman index. Clinical and pathological factors were compared using either Fisher’s exact test or Pearson’s χ2 test. Logistic regression analysis was performed to identify independent risk factors. Survival rate was calculated using the Kaplan-Meier method. RESULTS: SMGCs accounted for 10.9% of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers. These tumors were typically macroscopically elevated and histologically differentiated. There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location, tumor size, lymph node metastasis, the number of metastatic lymph nodes, venous invasion, or tumor stage (P = 0.052, P = 0.347, P = 0.595, P = 0.805, P = 0.559, and P = 0.408, respectively). Further, there was no significant difference in postoperative survival between the patient groups (P = 0.200). Of the 146 SMGC patients, a single patient had remnant cancer. CONCLUSION: A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC, and minimally invasive treatment may be indicated in some cases. PMID:24222960

  12. Relative Expression Analysis for Molecular Cancer Diagnosis and Prognosis

    PubMed Central

    Eddy, James A.; Sung, Jaeyun; Geman, Donald; Price, Nathan D.

    2010-01-01

    the potential to significantly contribute to molecular cancer diagnosis and prognosis. PMID:20218737

  13. Relative expression analysis for molecular cancer diagnosis and prognosis.

    PubMed

    Eddy, James A; Sung, Jaeyun; Geman, Donald; Price, Nathan D

    2010-04-01

    potential to significantly contribute to molecular cancer diagnosis and prognosis.

  14. Classification of breast cancer stroma as a tool for prognosis

    NASA Astrophysics Data System (ADS)

    Reis, Sara; Gazinska, Patrycja; Hipwell, John H.; Mertzanidou, Thomy; Naidoo, Kalnisha; Pinder, Sarah; Hawkes, David J.

    2016-03-01

    It has been shown that the tumour microenvironment plays a crucial role in regulating tumour progression by a number of different mechanisms, including the remodeling of collagen fibres in tumour-associated stroma. It is still unclear, however, if these stromal changes are of benefit to the host or the tumour. We hypothesise that stromal maturity is an important reflection of tumour biology, and thus can be used to predict prognosis. The aim of this study is to develop a texture analysis methodology which will automatically classify stromal regions from images of hematoxylin and eosin-stained (H and E) sections into two categories: mature and immature. Subsequently we will investigate whether stromal maturity could be used as a predictor of survival and also as a means to better understand the relationship between the radiological imaging signal and the underlying tissue microstructure. We present initial results for 118 regions-of-interest from a dataset of 39 patients diagnosed with invasive breast cancer.

  15. Arpin downregulation in breast cancer is associated with poor prognosis

    PubMed Central

    Lomakina, Maria E; Lallemand, François; Vacher, Sophie; Molinie, Nicolas; Dang, Irene; Cacheux, Wulfran; Chipysheva, Tamara A; Ermilova, Valeria D; de Koning, Leanne; Dubois, Thierry; Bièche, Ivan; Alexandrova, Antonina Y; Gautreau, Alexis

    2016-01-01

    Background: The Arp2/3 complex is required for cell migration and invasion. The Arp2/3 complex and its activators, such as the WAVE complex, are deregulated in diverse cancers. Here we investigate the expression of Arpin, the Arp2/3 inhibitory protein that antagonises the WAVE complex. Methods: We used qRT–PCR and reverse phase protein arrays in a patient cohort with known clinical parameters and outcome, immunofluorescence in breast biopsy cryosections and breast cancer cell lines. Results: Arpin was downregulated at the mRNA and protein levels in mammary carcinoma cells. Arpin mRNA downregulation was associated with poor metastasis-free survival (MFS) on univariate analysis (P=0.022). High expression of the NCKAP1 gene that encodes a WAVE complex subunit was also associated with poor MFS on univariate analysis (P=0.0037) and was mutually exclusive with Arpin low. Arpin low or NCKAP1 high was an independent prognosis factor on multivariate analysis (P=0.0012) and was strongly associated with poor MFS (P=0.000064). Conclusions: Loss of the Arp2/3 inhibitory protein Arpin produces a similar poor outcome in breast cancer as high expression of the NCKAP1 subunit of the Arp2/3 activatory WAVE complex. PMID:26867158

  16. Genetic susceptibility variants associated with colorectal cancer prognosis.

    PubMed

    Abulí, Anna; Lozano, Juan José; Rodríguez-Soler, María; Jover, Rodrigo; Bessa, Xavier; Muñoz, Jenifer; Esteban-Jurado, Clara; Fernández-Rozadilla, Ceres; Carracedo, Angel; Ruiz-Ponte, Clara; Cubiella, Joaquín; Balaguer, Francesc; Bujanda, Luis; Reñé, Josep M; Clofent, Juan; Morillas, Juan Diego; Nicolás-Pérez, David; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Andreu, Montserrat; Castells, Antoni; Castellví-Bel, Sergi

    2013-10-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death among men and women in Western countries. Once a tumour develops, a differentiated prognosis could be determined by lifestyle habits or inherited and somatic genetic factors. Finding such prognostic factors will be helpful in order to identify cases with a shorter survival or at a higher risk of recurrence that may benefit from more intensive treatment and follow-up surveillance. Sixteen CRC genetic susceptibility variants were directly genotyped in a cohort of 1235 CRC patients recruited by the EPICOLON Spanish consortium. Univariate Cox and multivariate regression analyses were performed taking as primary outcomes overall survival (OS), disease-free survival and recurrence-free interval. Genetic variants rs9929218 at 16q22.1 and rs10795668 at 10p14 may have an effect on OS. The G allele of rs9929218 was linked with a better OS [GG genotype, genotypic model: hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.45-0.93, P = 0.0179; GG/GA genotypes, dominant model: HR = 0.66, 95% CI 0.47-0.94, P = 0.0202]. Likewise, the G allele of rs10795668 was associated with better clinical outcome (GG genotype, genotypic model: HR = 0.73, 95% CI 0.53-1.01, P = 0.0570; GA genotype, genotypic model: HR = 0.66, 95% CI 0.47-0.92, P = 0.0137; GG/GA genotypes, dominant model: HR = 0.68, 95% CI 0.50-0.94, P = 0.0194). In conclusion, CRC susceptibility variants rs9929218 and rs10795668 may exert some influence in modulating patient's survival and they deserve to be further tested in additional CRC cohorts in order to confirm their potential as prognosis or predictive biomarkers.

  17. Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

    PubMed

    Chu, Xin-Yi; Jiang, Ling-Han; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

    2017-07-14

    The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

  18. Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis

    PubMed Central

    Chu, Xin-Yi; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

    2017-01-01

    The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information. PMID:28708071

  19. Colorectal cancer screening in an expanding panorama of screening programmes.

    PubMed

    Hoff, Geir

    2010-08-01

    Cervical and breast cancer screening programmes have been introduced in times when both the professional requirements for evidence based medicine and public demand for quantification of benefits may have been less explicit. The World Health Organisation has recommended cancer screening only for cervix, breast and colorectal cancer (CRC) - the latter leaving health authorities with a choice between a multitude of screening methods of which the efficacy has been proven only for fecal occult blood testing (FOBT). Although we are far from seeing the perfect screening method and screening programme, cost effectiveness for CRC screening has been estimated at least as cost-effective as established programmes for cervix and breast cancer screening. Established and imminent screening programmes should be considered as natural platforms for randomised trial with commitment and responsibility to continuously improve the quality and effectiveness of the screening service provided. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2013-01-01

    Cancer prognosis is of keen interest for cancer patients, 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), though 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. PMID:23956026

  1. 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.

  2. Study of radiation induced cancers in a breast screening programme.

    PubMed

    León, A; Verdú, G; Cuevas, M D; Salas, M D; Villaescusa, J I; Bueno, F

    2001-01-01

    It is demonstrated that screening mammography programmes reduce breast cancer mortality considerably. Nevertheless, radiology techniques have an intrinsic risk, the most important being the late somatic effect of the induction of cancer. This study was carried out in order to evaluate the risk to the population produced by the Comunidad Valenciana Breast Screening Programme. All the calculations are carried out for two risk models, UNSCEAR 94 and NRPB 93. On the one hand, screening series detriments are investigated as a function of doses delivered and other parameters related to population structure and X ray equipment. On the other hand the radiation induced cancer probability for a woman who starts at 45 years and remains in the programme until 65 years old is calculated as a function of mammography units' doses and average compression breast thickness. Finally, risk comparison between a screening programme starting at 45 years old and another one starting at 50 years old is made.

  3. [Results of the Czech National Breast Cancer screening programme].

    PubMed

    Skovajsová, M; Májek, O; Daneš, J; Bartoňková, H; Ngo, O; Dušek, L

    2014-01-01

    Breast cancer screening based on mammography is an effective tool for lowering mortality rates from this disease. The organised and nationwide Breast Cancer Screening Programme has been underway in the Czech Republic since 2002. Monitoring of the programme is based on data from the Czech National Cancer Registry (CNCR), Breast Cancer Screening Registry, and the Czech National Reference Centre (CNRC). These data sources make it possible to evaluate early performance indicators according to international standards, and to monitor the cancer burden in the Czech population. The CNRC data allow us to document the high validity of the available data as well as to map non-organised mammography examinations (so-called opportunistic screening). Until the mid-1990s, breast cancer incidence and mortality rates saw a slight but continuous increase. In the last 15 years, however, incidence rates have grown more substantially; by contrast, mortality rates have stalled and even started to decline since the 2000s. In the mid-1990s, the proportion of cancers diagnosed at stage I was below 20%; this situation has dramatically improved since then, as more than 40% cases of breast cancer were diagnosed at stage I in 2011. Breast cancer screening coverage currently amounts to 50%; this value reached a plateau in the period 2007-2008, and unfortunately has not shown any further significant increase. Over the last few decades, the breast cancer burden among the Czech population has been significantly reduced - despite the growing incidence rates, mortality rates have decreased, which can be largely attributed to earlier detection of breast cancer based on the screening programme. Further improvements in the programmes effectiveness can only be achieved if the population coverage becomes higher; the programme of personalised invitations to mammography examinations, which was introduced in early 2014, should contribute to the accomplishment of this goal.

  4. Becoming ADEPT (Applying Diagnosis, Etiology, Prognosis, and Therapy Programme): delivering distance learning on evidence-based medicine for librarians.

    PubMed

    Hicks, A; Booth, A; Sawers, C

    1998-09-01

    Evidence-based medicine (EBM) brings new challenges and opportunities for librarians. However, their ability to respond to this agenda is constrained by their difficulties in acquiring the requisite new skills and techniques while continuing to work in a busy information practice setting. The authors describe a joint initiative, between a specialist evidence-based healthcare information unit and a regional library network, to deliver training materials using a mixed workshop and distance learning format. The Applying Diagnosis, Etiology, Prognosis, and Therapy filters (ADEPT) Programme draws upon research conducted at McMaster University, Canada and, using techniques adapted from the teaching evidence-based medicine paradigm, seeks to equip health care librarians with the skills and techniques required to support evidence-based practice locally. The authors describe the thinking behind the programme, its main features, the extensive evaluation mechanisms incorporated into the course, the results of the evaluation and the lessons learnt. They conclude with a description of the way forward for participants on the programme who are adapting their newly acquired knowledge to their work situations. Further planned developments from the course's designers are also outlined briefly.

  5. Glycosylation of plasma IgG in colorectal cancer prognosis

    PubMed Central

    Theodoratou, Evropi; Thaçi, Kujtim; Agakov, Felix; Timofeeva, Maria N.; Štambuk, Jerko; Pučić-Baković, Maja; Vučković, Frano; Orchard, Peter; Agakova, Anna; Din, Farhat V. N.; Brown, Ewan; Rudd, Pauline M.; Farrington, Susan M.; Dunlop, Malcolm G.; Campbell, Harry; Lauc, Gordan

    2016-01-01

    In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation. PMID:27302279

  6. MDM2 promoter polymorphism and pancreatic cancer risk and prognosis.

    PubMed

    Asomaning, Kofi; Reid, Amy E; Zhou, Wei; Heist, Rebecca S; Zhai, Rihong; Su, Li; Kwak, Eunice L; Blaszkowsky, Lawrence; Zhu, Andrew X; Ryan, David P; Christiani, David C; Liu, Geoffrey

    2008-06-15

    The mouse double minute 2 homologue (MDM2) -309T/G promoter polymorphism has been associated recently with the development and prognosis of a variety of tumors. The G allele is associated with increased affinity for Sp1 binding and higher MDM2 mRNA and protein levels, leading to diminished tumor suppressor activity of the p53 pathway. We hypothesized that the G allele is also associated with increased risk and worse outcome in pancreatic cancer. We evaluated the association between MDM2 309T/G and the risk of histologically confirmed pancreatic adenocarcinoma at Massachusetts General Hospital using unconditional logistic regression (123 cases and 372 controls). Complete overall survival and progression-free survival data were also available for 109 newly diagnosed patients. The adjusted odds ratios (95% confidence intervals) of pancreatic cancer associated with the MDM2 T/G and G/G genotypes compared with TT were 1.89 (1.20-2.99) and 2.07 (1.03-4.16), respectively (adjusting for age, gender, smoking status, and pack-years of smoking). In Cox proportional hazards model with the wild-type T/T genotype as the reference category and adjusting for stage, treatment, and performance status, both the heterozygous T/G and the homozygous G/G genotypes were associated with decreased progression-free survival [adjusted hazard ratio (95% confidence interval), 1.67 (0.98-2.84) for T/G and 2.28 (1.11-4.71) for G/G] and overall survival [2.64 (1.23-5.67) for T/G and 3.12 (1.22-7.91) for G/G]. The G allele of the MDM2 -309T/G polymorphism is associated with 2- to 3-fold increase risk and progression of pancreatic adenocarcinoma and a corresponding decrease in survival.

  7. Establishment of a cancer surveillance programme: the South African experience

    PubMed Central

    Singh, Elvira; Ruff, Paul; Babb, Chantal; Sengayi, Mazvita; Beery, Moira; Khoali, Lerato; Kellett, Patricia; Underwood, J Michael

    2015-01-01

    Cancer is projected to become a leading cause of morbidity and mortality in low-income and middle-income countries in the future. However, cancer incidence in South Africa is largely under-reported because of a lack of nationwide cancer surveillance networks. We describe present cancer surveillance activities in South Africa, and use the International Agency for Research on Cancer framework to propose the development of four population-based cancer registries in South Africa. These registries will represent the ethnic and geographical diversity of the country. We also provide an update on a cancer surveillance pilot programme in the Ekurhuleni Metropolitan District, and the successes and challenges in the implementation of the IARC framework in a local context. We examine the development of a comprehensive cancer surveillance system in a middle-income country, which might serve to assist other countries in establishing population-based cancer registries in a resource-constrained environment. PMID:26248849

  8. Tumor hypoxia, p53, and prognosis in cervical cancers.

    PubMed

    Haensgen, G; Krause, U; Becker, A; Stadler, P; Lautenschlaeger, C; Wohlrab, W; Rath, F W; Molls, M; Dunst, J

    2001-07-15

    The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n = 14), IIIB (n = 49), and IVA (n = 7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO(2) measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin > or =11 g/dl vs. 27% for hemoglobin <11 g/dl, p = 0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p = 0.01). Sixty of the 70

  9. Risking 'Safety': Breast Cancer, Prognosis, and the Strategic Enterprise of Life.

    PubMed

    Ehlers, Nadine

    2016-03-01

    Living in modern biopolitical risk culture might be seen as synonymous with living in prognosis time, in the sense that risk of illness is endlessly forecast (prognosticated) in the broad social arena. 'Safety,' in this context, is framed as the anticipatory guarding against risk or disease in order to 'make live.' Thinking of risk and safety in these ways is limited, however, in that the prognosis cannot account for the individual's life or death drama. This paper asks: how are we to understand the constellation of risk, prognosis, and safety in relation to 'the subject in breast cancer prognosis'?

  10. An assessment of oral cancer curricula in dental hygiene programmes: implications for cancer control.

    PubMed

    Thacker, K K; Kaste, L M; Homsi, K D; LeHew, C W

    2016-11-01

    To assess oral cancer prevention and early detection curricula in Illinois associate-degree dental hygiene programmes and highlight global health applications. An email invitation was sent to each Illinois associate-degree granting dental hygiene programme's oral cancer contact to participate in a survey via a SurveyMonkey™ link to a 21-item questionnaire. Questions elicited background information on each programme and inquired about curriculum and methods used for teaching oral cancer prevention and early detection. Eight of the 12 (67%) programmes responded. Three (37.5%) reported having a specific oral cancer curriculum. Five (62.5%) require students to perform examinations for signs and symptoms of oral cancer at each clinic visit. Variations exist across the programmes in the number of patients each student sees annually and the number of oral cancer examinations each student performs before graduation. Seven programmes (87.5%) conduct early detection screening in community settings. All programmes included risk assessment associated with tobacco. All other risk factors measured were treated inconsistently. Significant differences in training and experience were reported across Illinois dental hygiene programmes. Training is neither standardized nor uniformly comprehensive. Students' preparation for delivering prevention and early detection services to their patients could be strengthened to ensure competence including reflection of risk factors and behaviours in a global context. Regular review of curricular guidelines and programme content would help dental hygienists meet the expectations of the Crete Declaration on Oral Cancer Prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

    DTIC Science & Technology

    2016-10-01

    Biology PRINCIPAL INVESTIGATOR: Scott A. Tomlins, M.D., Ph.D. CONTRACTING ORGANIZATION: Regents of the University of Michigan Ann Arbor, MI 48109...Cancer to Inform on Prognosis and Disease Biology 5b. GRANT NUMBER W81XWH-15-1-0661 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...169,574/yr Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology Goal(s): Perform

  12. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes.

    PubMed

    Petitjean, A; Achatz, M I W; Borresen-Dale, A L; Hainaut, P; Olivier, M

    2007-04-02

    A large amount of data is available on the functional impact of missense mutations in TP53 and on mutation patterns in many different cancers. New data on mutant p53 protein function, cancer phenotype and prognosis have recently been integrated in the International Agency for Research on Cancer TP53 database (http://www-p53.iarc.fr/). Based on these data, we summarize here current knowledge on the respective roles of mutagenesis and biological selection of mutations with specific functional characteristic in shaping the patterns and phenotypes of mutations observed in human cancers. The main conclusion is that intrinsic mutagenicity rates, loss of transactivation activities, and to a lesser extent, dominant-negative activities are the main driving forces that determine TP53 mutation patterns and influence tumor phenotype. In contrast, current experimental data on the acquisition of oncogenic activities (gain of function) by p53 mutants are too scarce and heterogenous to assess whether this property has an impact on tumor development and outcome. In the case of inherited TP53 mutations causing Li-Fraumeni and related syndromes, the age at onset of some tumor types is in direct relation with the degree of loss of transactivation capacity of missense mutations. Finally, studies on large case series demonstrate that TP53 mutations are independent markers of bad prognosis in breast and several other cancers, and that the exact type and position of the mutation influences disease outcome. Further studies are needed to determine how TP53 haplotypes or loss of alleles interact with mutations to modulate their impact on cancer development and prognosis.

  13. The perceptions of physicians in southeast Nigeria on truth-telling for cancer diagnosis and prognosis.

    PubMed

    Nwankwo, Kenneth Chima; Ezeome, Emmanuel

    2011-06-01

    The perceptions of Nigerian physicians on truth-telling for cancer diagnosis and prognosis have not been widely studied. There is a need to know the perception of the doctors on truth telling so as to inform appropriate professional education on the subject. To ascertain the perceptions of the physicians on truth-telling for cancer diagnosis and prognosis. A cross-sectional study was done with a self-administered questionnaire to 228 physicians available in the clinics and seminars at the hospital between January and April 2010. A total of 173 questionnaires were returned. Eighty-one (46.8%) always, 54 (31.2%) generally, and 38 (22%) rarely disclose cancer diagnosis and favorable prognosis to patients. Only 7.5% would disclose the truth of the prognosis to patients when the cancer is advanced. Physicians' age, specialty, training in palliative care, and doctors' views on truth disclosure if he/she had cancer significantly influenced the doctors' practice of truth-telling for cancer diagnosis. The physicians who treat cancer patients in southeast Nigeria tend to practice truth-telling for cancer diagnosis but not for a poor prognosis. Most of the physicians need training in physician-patient communication.

  14. A regional programme to improve skin cancer management.

    PubMed

    McGeoch, Graham R; Sycamore, Mark J; Shand, Brett I; Simcock, Jeremy W

    2015-12-01

    In 2008, public specialist and general practice services in Canterbury were unable to manage demand for skin cancer treatment. Local clinicians decided the solution was to develop a see-and-treat skin excision clinic staffed by plastic surgeons and general practitioners (GPs), and the introduction of subsidised excisions in general practice. This paper describes the collaboration between clinicians, managers and funders and the results and quality management measures of these initiatives. There is an increasing incidence of skin cancer. GPs in Canterbury were unable to meet increasing demand for skin cancer treatment because some lacked confidence and competence in skin cancer management. There was no public funding for primary care management of skin cancer, driving patients to fully funded secondary care services. Secondary care services were at capacity, with no coordinated programme across primary and secondary care. The programme has resulted in a greater number of skin cancers being treated by the public health system, a reduction in waiting times for treatment, and fewer minor skin lesions being referred to secondary care. Quality measures have been achieved and are improving steadily. Development of the programme has improved working relationships between primary and secondary care clinicians. The strategy was to facilitate the working relationship between primary and secondary care and increase the capacity for skin lesion excisions in both sectors. Skin cancer management can be improved by a coordinated approach between primary and secondary care.

  15. Does buccal cancer have worse prognosis than other oral cavity cancers?

    PubMed

    Camilon, P Ryan; Stokes, William A; Fuller, Colin W; Nguyen, Shaun A; Lentsch, Eric J

    2014-06-01

    To determine whether buccal squamous cell carcinoma has worse overall survival (OS) and disease-specific survival (DSS) than cancers in the rest of the oral cavity. Retrospective analysis of a large population database. We began with a Kaplan-Meier analysis of OS and DSS for buccal versus nonbuccal tumors with unmatched data, followed by an analysis of cases matched for race, age at diagnosis, stage at diagnosis, and treatment modality. This was supported by a univariate Cox regression comparing buccal cancer to nonbuccal cancer, followed by a multivariate Cox regression that included all significant variables studied. With unmatched data, buccal cancer had significantly lesser OS and DSS values than cancers in the rest of the oral cavity (P < .001). After case matching, the differences between OS and DSS for buccal cancer versus nonbuccal oral cancer were no longer significant. Univariate Cox regression models with respect to OS and DSS showed a significant difference between buccal cancer and nonbuccal cancer. However, with multivariate analysis, buccal hazard ratios for OS and DSS were not significant. With the largest series of buccal carcinoma to date, our study concludes that the OS and DSS of buccal cancer are similar to those of cancers in other oral cavity sites once age at diagnosis, tumor stage, treatment, and race are taken into consideration. The previously perceived poor prognosis of buccal carcinoma may be due to variations in tumor presentation, such as later stage and older patient age. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  16. BMI and breast cancer prognosis benefit: mammography screening reveals differences between normal weight and overweight women.

    PubMed

    Crispo, Anna; Grimaldi, Maria; D'Aiuto, Massimiliano; Rinaldo, Massimo; Capasso, Immacolata; Amore, Alfonso; D'Aiuto, Giuseppe; Giudice, Aldo; Ciliberto, Gennaro; Montella, Maurizio

    2015-02-01

    Few studies are available on the potential impact of body weight on breast cancer prognosis in screen-detected patients. Moreover, it is not known whether body mass index (BMI) could have a different prognostic impact in screen-detected versus symptomatic breast cancer patients. To investigate these unsolved issues, we carried out a retrospective study evaluating the effect of BMI on breast cancer prognosis in screen-detected vs symptomatic breast cancer patients. We conducted a follow-up study on 448 women diagnosed with incident, histologically-confirmed breast cancer. Patients were categorized according to their BMI as normal weight, overweight and obese. Disease free survival (DFS), overall survival (OS), and BMI curves were compared according to mode of cancer detection. Among screen-detected patients, higher BMI was associated with a significant lower DFS, whereas no significant difference was observed among symptomatic patients. OS showed similar results. In the multivariate analysis adjusting for age, education, tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR) and menopausal status, the risk for high level of BMI among screen-detected patients did not reach the statistical significance for either recurrence or survival. Our study highlights the potential impact of high bodyweight in breast cancer prognosis, the findings confirm that obesity plays a role in women breast cancer prognosis independently from diagnosis mode. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer?

    PubMed Central

    Shuwen, Han; Xi, Yang

    2017-01-01

    Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies. PMID:28408773

  18. Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity.

    PubMed

    Jochems, Caroline; Schlom, Jeffrey

    2011-05-01

    Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous groups. Analyses of immune infiltrate of several other carcinoma types also showed general correlations between immune infiltrate and prognosis, but with some conflicting results. This review will attempt to summarize the current state of this field and point out what factors may be responsible for some of the conflicting findings. Nonetheless, the breadth of reports drawing similar conclusions for some cancer cell types leads one to more seriously consider the link between immune cell infiltrate and tumor prognosis and/or response to therapy, and the potential for combining conventional cancer therapy with active immunotherapy employing therapeutic cancer vaccines.

  19. Computer-aided prognosis on breast cancer with hematoxylin and eosin histopathology images: A review.

    PubMed

    Chen, Jia-Mei; Li, Yan; Xu, Jun; Gong, Lei; Wang, Lin-Wei; Liu, Wen-Lou; Liu, Juan

    2017-03-01

    With the advance of digital pathology, image analysis has begun to show its advantages in information analysis of hematoxylin and eosin histopathology images. Generally, histological features in hematoxylin and eosin images are measured to evaluate tumor grade and prognosis for breast cancer. This review summarized recent works in image analysis of hematoxylin and eosin histopathology images for breast cancer prognosis. First, prognostic factors for breast cancer based on hematoxylin and eosin histopathology images were summarized. Then, usual procedures of image analysis for breast cancer prognosis were systematically reviewed, including image acquisition, image preprocessing, image detection and segmentation, and feature extraction. Finally, the prognostic value of image features and image feature-based prognostic models was evaluated. Moreover, we discussed the issues of current analysis, and some directions for future research.

  20. 'Hitting you over the head': oncologists' disclosure of prognosis to advanced cancer patients.

    PubMed

    Gordon, Elisa J; Daugherty, Christopher K

    2003-04-01

    The disclosure of prognosis to terminally ill patients has emerged as a recent concern given greater demands for patient involvement in medical decision-making in the United States. As part of the informed consent process, American physicians are legally and ethically obligated to provide information to such patients about risks, benefits, and alternatives of all available treatment options including the use of experimental therapies. Although not legally required, the disclosure of terminal prognosis is ethically justified because it upholds the principle of self-determination and enables patients to make treatment decisions consistent with their life goals. To understand oncologists' attitudes about disclosing prognostic information to cancer patients with advanced disease, we interviewed fourteen oncologists and conducted one focus group of medical fellows. Although oncologists reported to disclose prognosis in terms of cancer not being curable, they tend to avoid using percentages to convey prognosis. Oncologists' reported reluctance to disclosing prognosis was conveyed through the use of metaphors depicting the perceived violent impact of such information on patients. Oncologists' reluctance to disclose prognosis and preserve patient hope are held in check by their need to ensure that patients have 'realistic expectations' about therapy. We discuss these data in light of the cultural, ethical, and legal dimensions of prognosis disclosure, patient hope and the doctor-patient relationship, and recommend ways to enhance the communication process.

  1. Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

    SciTech Connect

    Bian, Yongqian; Wang, Li; Lu, Huanyu; Yang, Guodong; Zhang, Zhang; Fu, Haiyan; Lu, Xiaozhao; Wei, Mengying; Sun, Jianyong; Zhao, Qingchuan; Dong, Guanglong; Lu, Zifan

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer QKI expression is decreased in gastric cancer samples. Black-Right-Pointing-Pointer Promoter hyper methylation contributes to the downregulation of QKI. Black-Right-Pointing-Pointer QKI inhibits the growth of gastric cancer cells. Black-Right-Pointing-Pointer Decreased QKI expression predicts poor survival. -- Abstract: Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.

  2. Lower body mass index predicts worse cancer-specific prognosis in octogenarians with colorectal cancer.

    PubMed

    Adachi, Tomohiro; Hinoi, Takao; Kinugawa, Yusuke; Enomoto, Toshiyuki; Maruyama, Satoshi; Hirose, Hajime; Naito, Masanori; Tanaka, Keitaro; Miyake, Yasuhiro; Watanabe, Masahiko

    2016-08-01

    High body mass index (BMI) is a risk factor for colorectal cancer. However, the prognostic impact of BMI and other factors may differ between elderly and younger colorectal cancer patients. We analyze here prognostic factors in the surgical management of octogenarians with colorectal cancer and clarify the prognostic impact of BMI. Cox regression analysis and propensity score methods were used to retrospectively examine the association of BMI with mortality in 1613 octogenarian patients who underwent curative surgery for stage 0-III colorectal cancer. In the Cox regression analysis, lower BMI (<18.5 kg/m(2); p = 0.001), age ≥83 years (p = 0.008), American Society of Anesthesiology class ≥3: (p = 0.001), performance status ≥2 (p = 0.003), Union for International Cancer Control (UICC) stage ≥III (p = 0.001), and postoperative adverse events (p = 0.001) were independently associated with decreased overall survival. Lower BMI (p = 0.001) and UICC stage ≥III (p = 0.001) were independently associated with decreased cancer-specific survival. After covariate adjustment, lower BMI was a risk factor for overall [hazard ratio (HR) 1.62; 95 % confidence interval (CI) 1.26-2.05; p = 0.0004] and cancer-specific survival (HR 2.00; 95 % CI 1.39-2.87; p = 0.0038) compared with normal BMI (18.5-24.9 kg/m(2)). Lower BMI is significantly and independently associated with increased mortality risk in octogenarians who undergo curative surgery for colorectal cancer. Lower BMI should be used for prognosis assessment in octogenarians with colorectal cancer.

  3. Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression.

    PubMed

    Igarashi, Takamichi; Araki, Kenichiro; Yokobori, Takehiko; Altan, Bolag; Yamanaka, Takahiro; Ishii, Norihiro; Tsukagoshi, Mariko; Watanabe, Akira; Kubo, Norio; Handa, Tadashi; Hosouchi, Yasuo; Nishiyama, Masahiko; Oyama, Tetsunari; Shirabe, Ken; Kuwano, Hiroyuki

    2017-02-14

    Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed. Furthermore, RAB5 suppression analysis by siRNA was performed to determine the roles of RAB5 in morphological change, proliferation potency, cell migration ability, and invasiveness of the pancreatic cancer cell line.High RAB5 expression correlated with the presence of lymphatic invasion and venous invasion and low E-cadherin expression. Patients with high RAB5 expression had a poorer prognosis than those with low RAB5 expression. RAB5 suppression in pancreatic cancer cells enhanced E-cadherin expression; changed cell morphology from spindle to round; and inhibited proliferation, invasion, and cell migration.RAB5 contributes to poor prognosis and progression in pancreatic cancer patients. It may be a promising candidate for individualized therapy in refractory pancreatic cancer.

  4. Building capacity for sustainable research programmes for cancer in Africa.

    PubMed

    Adewole, Isaac; Martin, Damali N; Williams, Makeda J; Adebamowo, Clement; Bhatia, Kishor; Berling, Christine; Casper, Corey; Elshamy, Karima; Elzawawy, Ahmed; Lawlor, Rita T; Legood, Rosa; Mbulaiteye, Sam M; Odedina, Folakemi T; Olopade, Olufunmilayo I; Olopade, Christopher O; Parkin, Donald M; Rebbeck, Timothy R; Ross, Hana; Santini, Luiz A; Torode, Julie; Trimble, Edward L; Wild, Christopher P; Young, Annie M; Kerr, David J

    2014-05-01

    Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced-based cancer control approaches and planning at the local, regional and national levels.

  5. Feasibility of an exercise rehabilitation programme for cancer patients.

    PubMed

    Stevinson, C; Fox, K R

    2006-09-01

    A growing body of evidence indicates the benefits of exercise as a rehabilitation intervention for cancer patients. However, few hospitals offer exercise-based rehabilitation programmes to patients. This study evaluated the feasibility and acceptability of a group-based exercise programme for cancer patients attending a local oncology centre. The intervention consisted of a weekly instructor-led circuit training class supplemented by home-based activity 4 days/week for 10 weeks. From 28 eligible patients, 12 were recruited (43%), of whom nine completed the intervention (75%). The three withdrawals were due to worsening of disease. Adherence (mean of 7.5 classes attended and 4 days/week of home activity performed) and tolerability (no adverse events) were good. Positive features of the programme identified in interviews with participants included the variety and scope of the exercises, and the empathetic but positive approach of the instructors. The small group format was highly valued with participants receiving social support and inspiration from each other. Perceived outcomes included improved fitness, reduced fatigue, enjoyment, enhanced mood and a sense of achievement. Several participants felt that the intervention represented a stepping stone to becoming habitual exercisers. Results suggested that the programme was feasible and acceptable to patients, but uptake was low, indicating a need for more effective recruitment strategies in order for a cost-effective service to be implemented.

  6. Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype.

    PubMed

    Kida, Kumiko; Ishikawa, Takashi; Yamada, Akimitsu; Shimada, Kazuhiro; Narui, Kazutaka; Sugae, Sadatoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Ichikawa, Yasushi; Endo, Itaru

    2016-04-01

    Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

  7. Prognosis of synchronous bilateral breast cancer: a review and meta-analysis of observational studies.

    PubMed

    Holm, Marianne; Tjønneland, Anne; Balslev, Eva; Kroman, Niels

    2014-08-01

    Currently, no consistent evidence-based guidelines for the management of synchronous bilateral breast cancer (SBBC) exist and it is uncertain how presenting with SBBC affects patients' prognosis. We conducted a review of studies analyzing the association between SBBC and prognosis. The studies that reported adjusted effect measures were included in meta-analyses of effect of bilaterality on breast cancer mortality. From 57 initially identified records 17 studies from 11 different countries including 8,050 SBBC patients were included. The quality of the studies varied but was generally low with small sample sizes, and lack of consistent, detailed histo-pathological information. When doing meta-analysis on the subgroup of studies that provided adjusted effect estimates on breast cancer mortality (nine studies including 3,631 SBBC cases), we found that bilaterality in itself had a negative impact on prognosis after adjustment for known prognostic factors (pooled HR 1.37, 95 % CI 1.24-1.50, p < 0.0001). Multiple sensitivity analyses indicated robustness of the overall estimate. This review summarizes the current evidence of the association between SBBC and prognosis. The previously accepted convention that appropriate adjuvant treatment can be determined by considering the higher risk cancer was not confirmed in this review; rather it seems that being diagnosed with two tumors simultaneously entails a worse prognosis above and beyond that of the unilateral cancers of the same stage. To determine the true association between SBBC and breast cancer prognosis, studies of large and updated samples of SBBC should be done and include thorough histo-pathologic information.

  8. MET4 Expression Predicts Poor Prognosis of Gastric Cancers with Helicobacter pylori Infection.

    PubMed

    Sakamoto, Naoko; Tsujimoto, Hironori; Takahata, Risa; Brian, Cao; Ping, Zhao; Ito, Nozomi; Shimazaki, Hideyuki; Ichikura, Takashi; Hase, Kazuo; Vande Woude, George F; Shinomiya, Nariyoshi

    2016-12-23

    Role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4-positive gastric cancers showed poorer prognosis than MET4-negative cases (overall survival, P = 0.02; relapse-free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori-positive cases (overall survival, P < 0.01; relapse-free survival, P = 0.01) but not in H. pylori-negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of worst prognosis. Stimulation of MET-positive gastric cancer cells with live H. pylori bacteria directly up-regulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti-apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. H. pylori stimulated MET-positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti-apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy. This article is protected by copyright. All rights reserved.

  9. DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.

    PubMed

    Powe, Desmond G; Dhondalay, Gopal Krishna R; Lemetre, Christophe; Allen, Tony; Habashy, Hany O; Ellis, Ian O; Rees, Robert; Ball, Graham R

    2014-01-01

    Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p<0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is

  10. DACH1: Its Role as a Classifier of Long Term Good Prognosis in Luminal Breast Cancer

    PubMed Central

    Lemetre, Christophe; Allen, Tony; Habashy, Hany O.; Ellis, Ian O.; Rees, Robert; Ball, Graham R.

    2014-01-01

    Background Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. Materials and methods A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Results Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and ‘luminal-like’ markers of good prognosis including FOXA1 and RERG (p<0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Conclusion Nuclear DACH1 expression appears to be a

  11. Sixteen-kinase gene expression identifies luminal breast cancers with poor prognosis.

    PubMed

    Finetti, Pascal; Cervera, Nathalie; Charafe-Jauffret, Emmanuelle; Chabannon, Christian; Charpin, Colette; Chaffanet, Max; Jacquemier, Jocelyne; Viens, Patrice; Birnbaum, Daniel; Bertucci, François

    2008-02-01

    Breast cancer is a heterogeneous disease made of various molecular subtypes with different prognosis. However, evolution remains difficult to predict within some subtypes, such as luminal A, and treatment is not as adapted as it should be. Refinement of prognostic classification and identification of new therapeutic targets are needed. Using oligonucleotide microarrays, we profiled 227 breast cancers. We focused our analysis on two major breast cancer subtypes with opposite prognosis, luminal A (n = 80) and basal (n = 58), and on genes encoding protein kinases. Whole-kinome expression separated luminal A and basal tumors. The expression (measured by a kinase score) of 16 genes encoding serine/threonine kinases involved in mitosis distinguished two subgroups of luminal A tumors: Aa, of good prognosis and Ab, of poor prognosis. This classification and its prognostic effect were validated in 276 luminal A cases from three independent series profiled across different microarray platforms. The classification outperformed the current prognostic factors in univariate and multivariate analyses in both training and validation sets. The luminal Ab subgroup, characterized by high mitotic activity compared with luminal Aa tumors, displayed clinical characteristics and a kinase score intermediate between the luminal Aa subgroup and the luminal B subtype, suggesting a continuum in luminal tumors. Some of the mitotic kinases of the signature represent therapeutic targets under investigation. The identification of luminal A cases of poor prognosis should help select appropriate treatment, whereas the identification of a relevant kinase set provides potential targets.

  12. [De novo cancer after solid organ transplantation: Epidemiology, prognosis and management].

    PubMed

    Guillemin, Aude; Rousseau, Benoît; Neuzillet, Cindy; Joly, Charlotte; Boussion, Helene; Grimbert, Philippe; Compagnon, Philippe; Duvoux, Christophe; Tournigand, Christophe

    2017-03-01

    The risk of cancer after solid organ transplantation is increased by 2.6 compared to overall population. Cancer is currently the third leading cause of death in solid organ transplanted patients, making screening and early management of de novo cancers a major challenge. This increased risk of cancer in this population results from the combination of known environmental risk factors of cancer, comorbidities of transplanted patients, and exposure to chronic immunosuppression. The prognosis of cancer in these patients seems poorer as compared to other cancer patients owing to their comorbidities, the immunosuppression and patient's poorer tolerance to oncologic treatment. Moreover, interactions between immunosuppressive agents and antitumor therapies must be taken into account in the therapeutic strategy. Better knowledge of the specificities of solid organ transplanted patients with de novo cancer is required to improve cancer care in this patient population. This article aims to review the current data available on de novo cancers in solid organ transplanted patients, with a focus on epidemiology, risks factors of de novo cancers, impact of immunosuppressive drugs and oncologic prognosis.

  13. The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

    PubMed

    Hong, Sung Pil; Min, Byung So; Kim, Tae Il; Cheon, Jae Hee; Kim, Nam Kyu; Kim, Hoguen; Kim, Won Ho

    2012-05-01

    Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. CYB5R1 links epithelial-mesenchymal transition and poor prognosis in colorectal cancer

    PubMed Central

    Lamprecht, Sebastian; Engel, Jutta; Hermeking, Heiko; Kirchner, Thomas; Horst, David

    2016-01-01

    Colorectal cancers show significant tumor cell heterogeneity within the same core genetic background. Epithelial-mesenchymal transition (EMT) is an important functional aspect of this heterogeneity and hallmark of colorectal cancer progression. Here, we identify CYB5R1, an enzyme involved in oxidative stress protection and drug metabolism, as an indicator of EMT in colon cancer. We demonstrate high CYB5R1 expression in colorectal cancer cells undergoing EMT at the infiltrative tumor edge and reveal an extraordinarily strong association of CYB5R1 expression with two core EMT gene expression signatures in a large independent colon cancer data set from The Cancer Genome Atlas (TCGA). Furthermore, we demonstrate that CYB5R1 is required for an infiltrative tumor cell phenotype, and robustly linked with poor prognosis in colorectal cancer. Our findings have important implications for colon cancer cells undergoing EMT and may be exploited for diagnostic and therapeutic purposes. PMID:27120783

  15. Non-coding RNAs as clinical biomarkers for cancer diagnosis and prognosis.

    PubMed

    Mishra, Prasun J

    2014-11-01

    Developing more precise diagnostics approaches to predict cancer progression and prognosis is the key to precision medicine. Overwhelming evidence now suggests that small non-coding RNAs such as miRNAs can be useful tools as biomarkers for molecular diagnostics. miRNAs can serve as biomarkers in a variety of diseases, such as neurological disorders, cardiovascular disease, Type II diabetes, cancer and so on. miRNAs can not only be utilized for monitoring treatment but also for patient stratification and hence are promising predictive biomarkers in cancer progression and prognosis, as well as in predicting drug response. This article focuses on some of the recent findings in the field of miRNA biomarkers and discusses its implications for cancer diagnostics and precision medicine.

  16. MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis*

    PubMed Central

    Xie, Qiu-ping; Xiang, Cheng; Wang, Gang; Lei, Ke-feng; Wang, Yong

    2016-01-01

    In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC. PMID:27143263

  17. MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis.

    PubMed

    Xie, Qiu-Ping; Xiang, Cheng; Wang, Gang; Lei, Ke-Feng; Wang, Yong

    2016-05-01

    In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC.

  18. Global histone post-translational modifications and cancer: Biomarkers for diagnosis, prognosis and treatment?

    PubMed Central

    Khan, Shafqat Ali; Reddy, Divya; Gupta, Sanjay

    2015-01-01

    Global alterations in epigenetic landscape are now recognized as a hallmark of cancer. Epigenetic mechanisms such as DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs are proven to have strong association with cancer. In particular, covalent post-translational modifications of histone proteins are known to play an important role in chromatin remodeling and thereby in regulation of gene expression. Further, histone modifications have also been associated with different aspects of carcinogenesis and have been studied for their role in the better management of cancer patients. In this review, we will explore and discuss how histone modifications are involved in cancer diagnosis, prognosis and treatment. PMID:26629316

  19. [Colorectal cancer screening programme in Aragon (Spain): preliminary results].

    PubMed

    Solé Llop, Mª Esther; Cano Del Pozo, Mabel; García Montero, José-Ignacio; Carrera-Lasfuentes, Patricia; Lanas, Ángel

    2017-08-04

    To describe preliminary findings from the colorectal cancer screening programme in Aragon (Spain) to evaluate its implementation. We have collected data from the first year of the program (2014) based on faecal occult blood immunochemical (FOBTi) test in patients 60-69 years old. We report "indicators" defined by the "Red Nacional de Cribado". Invited population after exclusions: 12,518. Program participation rate: 45.28% (95%CI: 44.41-46.15). Inadequate tests: 0.21% (95%CI: 0.12-0.37); positive FOBTi test 10.75% (95%CI: 9.97-11.58) and colonoscopy acceptance 95.07% (95%CI: 93.04-96.52). Colonoscopy was appropriate and complete in 97.58% (95%CI: 95.98-98.55) of cases. The high- and low-risk adenoma detection rates were 14.7‰ (95%CI: 11.9-18.2) and 5.55‰ (95%CI: 3.9-7.8) respectively. The positive predictive value for any adenoma was 58.55% (95%CI: 54.49-62.49) and for invasive cancer was 5.36% (95%CI: 3.8-7.51). The indicator analysis of the ongoing programme suggests the programme is being implemented correctly in our community. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

    PubMed

    Baumgärtner, A K; Häusler, A; Seifert-Klauss, V; Schuster, T; Schwarz-Boeger, U; Kiechle, M

    2011-10-01

    Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p<0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55-1.19, p=0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45-1.02, p=0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57-6.91, p=0.28 and HR 4.59, 95%CI 0.91-23.25, p=0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

  1. Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer

    PubMed Central

    Zhang, Weijing; Li, Han; Ou, Yulan; Song, Libing

    2017-01-01

    Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients. PMID:28758939

  2. The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking.

    PubMed

    Robertson, Claire

    2016-04-10

    The extracellular matrix in the healthy breast has an important tumor suppressive role, whereas the abnormal ECM in tumors can promote aggressiveness, and has been linked to breast cancer relapse, survival and resistance to chemotherapy. This review article gives an overview of the elements of the ECM which have been linked to prognosis of breast cancers, including changes in ECM protein composition, splicing, and microstructure.

  3. Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

    PubMed Central

    Grewal, Jai; Kesari, Santosh

    2008-01-01

    Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also correlate with prognosis. PMID:18373884

  4. Characteristics and prognosis of breast cancer in younger women.

    PubMed

    Dirier, A; Burhanedtin-Zincircioglu, S; Karadayi, B; Isikdogan, A; Aksu, R

    2009-01-01

    Women under 40 years of age comprise a small proportion of patients with breast cancer. Clinical and pathological features of the disease in these patients are different from those in older patients with this type of cancer. In the present study we investigated the clinicopathological characteristics and prognostic factors in young patients with breast cancer. We retrospectively reviewed the medical records of 249 consecutive breast cancer patients who were admitted to our department between August 2001 and December 2005. Clinicopathological features were determined both in patients under and over 40 years of age. 106 (42.5%) patients were under and 143 (57.5%) were over 40 years. The mean age was 35.2 years for those under 40 years and 54 for those older than 40 years. At diagnosis, 10.4% of the patients in the younger age group and 7.0% in the older age group had metastasis (p=0.500). Patients in the younger age group exhibited higher estrogen receptor (ER) negativity (48.1 vs. 37.1%) (p=0.425) and a higher percentage of family history of breast cancer (4.7 vs. 2.8%) (p=0.651). Breast cancer in younger women was more frequently associated with other poor prognostic factors such as perineural and/or lymphovascular invasion. The 5-year overall survival was 6.3% for the younger patients and 22.2% for the older ones (p=0.004). This study demonstrates that breast cancer in younger patients has significantly more poor prognostic features compared to older ones.

  5. Clinicopathological characteristics and prognosis of alpha-fetoprotein positive gastric cancer in Chinese patients

    PubMed Central

    Wang, Daguang; Li, Chunping; Xu, Yuechao; Xing, Yanpeng; Qu, Limei; Guo, Yuchen; Zhang, Yang; Sun, Xuan; Suo, Jian

    2015-01-01

    Purpose: This study aimed to review the clinicopathological, histochemical, and prognostic features of Alpha-Fetoprotein (AFP) positive gastric cancer. Patients and methods: Six hundred and fifty one patients with gastric cancer who underwent gastrectomy between January 2009 and December 2012 at The First Hospital of Jilin University were enrolled in the study. Among them, 45 patients were identified as AFP positive gastric cancer. The clinicopathologic characteristics and prognosis of the AFP positive gastric cancer patients were analyzed. Results: Among the 45 AFP positive patients, serum levels of AFP were < 100 µg/L in nine patients. The histological classification of 45 patients was as follows: hepatoid type, 25 (55.6%) cases; fetal gastrointestinal type, 12 (26.7%) cases; yolk sac tumor type, 2 (4.4%) cases; and mixed type, 6 (13.3%) cases. Twenty nine (64.4%) cases were AFP positive by immunohistochemical analysis; we found no significant difference in AFP positivity and histologic type. However, the differences in the number of metastasis lymph nodes, the maximum tumor diameter, pathological stage, vascular invasion and liver metastasis between the AFP positive group and the negative group were significant. At the same T stage, the liver metastasis status of the AFP positive group was higher than that of the negative group. The AFP positive group had a much poorer prognosis than the negative group. Conclusion: AFP positive gastric cancer is associated with aggressive behavior and poorer prognosis compared to that of AFP negative gastric cancer. PMID:26261510

  6. B7-H4 is Predictive of Poor Prognosis in Patients with Gastric Cancer

    PubMed Central

    Cui, YongHui; Li, ZhiHan

    2016-01-01

    Background Recently, some studies were performed to evaluate the relevance of B7-H4 and gastric cancer (GC) prognosis. However, the results remained controversial. Therefore, we performed the present meta-analysis. Material/Methods We performed a systematic search in PubMed and Web of Science databases. All data were extracted and reviewed from each eligible study independently by 2 investigators. The strength of association between B7-H4 and GC prognosis was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI). Results Six studies that evaluated the association between B7-H4 and GC prognosis were included. The results showed a statistically significant association of B7-H4 and GC prognosis (OR=1.63, 95%CI=1.30–2.03). Furthermore, we conducted subgroup analysis based on source of B7-H4; the results from blood (OR=1.71; 95%CI, 1.09–2.68) and tissue (OR=1.60; 95%CI, 1.03–2.07) indicated B7-H4 was significantly associated with poor prognosis. Conclusions This meta-analysis suggests that GC patients with high B7-H4 have poor prognosis. PMID:27820598

  7. Prostate cancer between prognosis and adequate/proper therapy

    PubMed Central

    Grozescu, T; Popa, F

    2017-01-01

    Knowing the indolent, non-invasive nature of most types of prostate cancer, as well as the simple fact that the disease seems more likely to be associated with age rather than with other factors (50% of men at the age of 50 and 80% at the age of 80 have it [1], with or without presenting any symptom), the big challenge of this clinical entity was to determine severity indicators (so far insufficient) to guide the physician towards an adequate attitude in the clinical setting. The risk of over-diagnosing and over-treating many prostate cancer cases (indicated by all the major European and American studies) is real and poses many question marks. The present paper was meant to deliver new research data and to reset the clinical approach in prostate cancer cases. PMID:28255369

  8. Colorectal Cancer Prognosis Following Obesity Surgery in a Population-Based Cohort Study.

    PubMed

    Tao, Wenjing; Konings, Peter; Hull, Mark A; Adami, Hans-Olov; Mattsson, Fredrik; Lagergren, Jesper

    2017-05-01

    Obesity surgery involves mechanical and physiological changes of the gastrointestinal tract that might promote colorectal cancer progression. Thus, we hypothesised that obesity surgery is associated with poorer prognosis in patients with colorectal cancer. This nationwide population-based cohort study included all patients with an obesity diagnosis who subsequently developed colorectal cancer in Sweden from 1980 to 2012. The exposure was obesity surgery, and the main and secondary outcomes were disease-specific mortality and all-cause mortality, respectively. Cox proportional hazard survival models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for sex, age, calendar year and education level. The exposed and unexposed cohort included 131 obesity surgery and 1332 non-obesity surgery patients with colorectal cancer. There was a statistically significant increased rate of colorectal cancer deaths following obesity surgery (disease-specific HR 1.50, 95% CI 1.00-2.19). When analysed separately, the mortality rate was more than threefold increased in rectal cancer patients with prior obesity surgery (disease-specific HR 3.70, 95% CI 2.00-6.90), while no increased mortality rate was found in colon cancer patients (disease-specific HR 1.10, 85% CI 0.67-1.70). This population-based study among obese individuals found a poorer prognosis in colorectal cancer following obesity surgery, which was primarily driven by the higher mortality rate in rectal cancer.

  9. The role of pleomorphic adenoma gene-like 2 in gastrointestinal cancer development, progression, and prognosis.

    PubMed

    Liu, Bo; Lu, Chong; Song, Yong-Xi; Gao, Peng; Sun, Jing-Xu; Chen, Xiao-Wan; Wang, Mei-Xian; Dong, Yu-Lan; Xu, Hui-Mian; Wang, Zhen-Ning

    2014-01-01

    Numerous previous studies have revealed that pleomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that is active in cancer progression. The aim of this study was to investigate the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer. Immunohistochemical analysis revealed that PLAGL2 was expressed in gastrointestinal tumors and adjacent normal tissues. The expression of PLAGL2 was significantly higher in 225 colorectal cancer tissues than in 66 adjacent non-tumor tissues (P = 0.037). However, expression was not significantly different between 286 gastric tumors and 57 adjacent non-tumor tissues (P = 0.352). Moreover, the PLAGL2 expression level significantly correlated with the depth of tumor invasion in colorectal cancer (P = 0.030). However, the PLAGL2 expression level significantly correlated with tumor size in gastric cancer (P = 0.046). Furthermore, we performed survival analyses and found that neither higher nor lower PLAGL2 expression was a prognostic factor in gastrointestinal cancer. Our findings indicate that PALGL2 serves as a tumor oncoprotein in the development and progression of colorectal cancer. However, the role of this protein in the development, progression and prognosis of gastric cancer is uncertain. Further investigation into the molecular mechanisms of PLAGL2 activity in gastrointestinal cancer is warranted.

  10. Sex hormones and breast cancer risk and prognosis.

    PubMed

    Folkerd, Elizabeth; Dowsett, Mitch

    2013-08-01

    The study of large prospective collections of plasma samples from women prior to the development of breast cancer has firmly established certain sex steroids as being significantly associated with risk. The strongest associations have been found in postmenopausal women in whom the within person variability of most hormones is markedly reduced but some positive associations have also been seen in premenopausal women. Plasma estrogens show the strongest correlations with risk and these are strengthened by measurement or calculation of the proportion of estradiol that circulates free of sex hormone binding globulin (SHBG), consistent with this being the most active fraction. The relationships have been reported to potentially explain virtually all of the association of breast cancer with body mass index in postmenopausal women; this is likely to be due to non-ovarian estrogen synthesis being prominent in subcutaneous fat. These strong relationships have led to plasma and urine estrogen levels being used as intermediate end-points in the search for genes that affect breast cancer risk via their role in steroid disposition. Plasma androgen levels also show a relationship with breast cancer risk that is weakened but not eliminated by 'correction' for estrogen levels. This has been argued to be evidence of the local production of estrogens being important in the etiology of breast cancer. Given that plasma steroid levels do not correlate closely with mammographic density, which is strongly associated with risk, the opportunity exists to combine the two factors in assessing breast cancer risk but the low availability of suitable estrogen assays is a major impediment to this. In established breast cancer, plasma estrogens have been found to correlate with gene expression of estrogen dependent genes and the expression of these varies across the menstrual cycle of premenopausal women. There is infrequently a need for routine measurement of plasma estrogen levels but it has

  11. DHX32 expression is an indicator of poor breast cancer prognosis

    PubMed Central

    Wang, Meng; Zhang, Guojun; Wang, Yajie; Ma, Ruimin; Zhang, Limin; Lv, Hong; Fang, Fang; Kang, Xixiong

    2017-01-01

    Emerging evidence suggests that DEAH-box polypeptide 32 (DHX32) serves an important role in the progression and metastasis of cancer. However, the role of DHX32 in breast cancer remains to be completely elucidated. The aim of the present study was to evaluate the expression and clinical significance of DHX32 in breast cancer. The reverse transcription-quantitative polymerase chain reaction was performed to analyze DHX32 messenger (m)RNA expression, and western blotting and immunohistochemistry were performed to examine DHX32 protein expression in breast cancer and adjacent non-cancerous tissues. The association in breast cancer between DHX32 expression, clinicopathological features and prognosis was analyzed using 193 breast cancer tissue samples. The results of the present study demonstrated that breast cancer tissues exhibited increased DHX32 mRNA and protein expression compared with adjacent non-cancerous tissues (P<0.001). In addition, DHX32 expression was significantly associated with breast cancer clinical stage (P=0.006), histological grade (P=0.029), lymph node metastasis (P<0.001) and expression of the proliferation marker Ki-67 (P=0.004). Kaplan-Meier estimator analysis indicated that increased DHX32 expression is associated with poor prognosis in patients with breast cancer. Furthermore, the Cox proportional hazards model indicated that DHX32 expression is an independent prognostic factor for decreased overall survival and disease-free survival in patients with breast cancer. In conclusion, the results of the present study suggest that DHX32 overexpression is an unfavorable prognostic biomarker in breast cancer and a potential therapeutic target of future breast cancer treatments. PMID:28356982

  12. DHX32 expression is an indicator of poor breast cancer prognosis.

    PubMed

    Wang, Meng; Zhang, Guojun; Wang, Yajie; Ma, Ruimin; Zhang, Limin; Lv, Hong; Fang, Fang; Kang, Xixiong

    2017-02-01

    Emerging evidence suggests that DEAH-box polypeptide 32 (DHX32) serves an important role in the progression and metastasis of cancer. However, the role of DHX32 in breast cancer remains to be completely elucidated. The aim of the present study was to evaluate the expression and clinical significance of DHX32 in breast cancer. The reverse transcription-quantitative polymerase chain reaction was performed to analyze DHX32 messenger (m)RNA expression, and western blotting and immunohistochemistry were performed to examine DHX32 protein expression in breast cancer and adjacent non-cancerous tissues. The association in breast cancer between DHX32 expression, clinicopathological features and prognosis was analyzed using 193 breast cancer tissue samples. The results of the present study demonstrated that breast cancer tissues exhibited increased DHX32 mRNA and protein expression compared with adjacent non-cancerous tissues (P<0.001). In addition, DHX32 expression was significantly associated with breast cancer clinical stage (P=0.006), histological grade (P=0.029), lymph node metastasis (P<0.001) and expression of the proliferation marker Ki-67 (P=0.004). Kaplan-Meier estimator analysis indicated that increased DHX32 expression is associated with poor prognosis in patients with breast cancer. Furthermore, the Cox proportional hazards model indicated that DHX32 expression is an independent prognostic factor for decreased overall survival and disease-free survival in patients with breast cancer. In conclusion, the results of the present study suggest that DHX32 overexpression is an unfavorable prognostic biomarker in breast cancer and a potential therapeutic target of future breast cancer treatments.

  13. Raman microscopy in the diagnosis and prognosis of surgically resected nonsmall cell lung cancer

    NASA Astrophysics Data System (ADS)

    Magee, Nicholas David; Beattie, James Renwick; Carland, Chris; Davis, Richard; McManus, Kieran; Bradbury, Ian; Fennell, Dean Andrew; Hamilton, Peter William; Ennis, Madeleine; McGarvey, John Joseph; Elborn, Joseph Stuart

    2010-03-01

    The main curative therapy for patients with nonsmall cell lung cancer is surgery. Despite this, the survival rate is only 50%, therefore it is important to more efficiently diagnose and predict prognosis for lung cancer patients. Raman spectroscopy is useful in the diagnosis of malignant and premalignant lesions. The aim of this study is to investigate the ability of Raman microscopy to diagnose lung cancer from surgically resected tissue sections, and predict the prognosis of these patients. Tumor tissue sections from curative resections are mapped by Raman microscopy and the spectra analzsed using multivariate techniques. Spectra from the tumor samples are also compared with their outcome data to define their prognostic significance. Using principal component analysis and random forest classification, Raman microscopy differentiates malignant from normal lung tissue. Principal component analysis of 34 tumor spectra predicts early postoperative cancer recurrence with a sensitivity of 73% and specificity of 74%. Spectral analysis reveals elevated porphyrin levels in the normal samples and more DNA in the tumor samples. Raman microscopy can be a useful technique for the diagnosis and prognosis of lung cancer patients receiving surgery, and for elucidating the biochemical properties of lung tumors.

  14. High expression of FOXR2 in breast cancer correlates with poor prognosis.

    PubMed

    Song, Haiping; He, Wenshan; Huang, Xiaoqing; Zhang, Huiqiong; Huang, Tao

    2016-05-01

    Forkhead box protein R2 (FOXR2) is associated with human central nervous system neoplasms. However, the expression level of FOXR2 in breast cancer specimens remains largely unknown. To identify whether FOXR2 can serve as a biomarker for the diagnosis and prognosis of breast cancer, real-time PCR and immunohistochemistry (IHC) staining were utilized to detect the expression of FOXR2. The messenger RNA (mRNA) and protein levels of FOXR2 in breast cancer samples were novelty higher compared to non-tumorous breast tissues. IHC results revealed FOXR2 expression was significantly correlated to classifications tumor size (p = 0.007) and Ki-67 (p = 0.019). The patients with high expression of FOXR2 had a significantly poor prognosis compared to those of low expression (p = 0.003), especially in the patients with tumor size ≥2 cm (p = 0.006) and lymph node metastasis status (p = 0.004). Furthermore, multivariate analysis indicated that FOXR2 expression was an independent prognostic factor for breast cancer patients (p = 0.035). This study first identifies that FOXR2 may be an important molecular marker for diagnosis and prognosis of breast cancer.

  15. A network medicine approach to build a comprehensive atlas for the prognosis of human cancer.

    PubMed

    Zhang, Fan; Ren, Chunyan; Lau, Kwun Kit; Zheng, Zihan; Lu, Geming; Yi, Zhengzi; Zhao, Yongzhong; Su, Fei; Zhang, Shaojun; Zhang, Bin; Sobie, Eric A; Zhang, Weijia; Walsh, Martin J

    2016-11-01

    The Cancer Genome Atlas project has generated multi-dimensional and highly integrated genomic data from a large number of patient samples with detailed clinical records across many cancer types, but it remains unclear how to best integrate the massive amount of genomic data into clinical practice. We report here our methodology to build a multi-dimensional subnetwork atlas for cancer prognosis to better investigate the potential impact of multiple genetic and epigenetic (gene expression, copy number variation, microRNA expression and DNA methylation) changes on the molecular states of networks that in turn affects complex cancer survivorship. We uncover an average of 38 novel subnetworks in the protein-protein interaction network that correlate with prognosis across four prominent cancer types. The clinical utility of these subnetwork biomarkers was further evaluated by prognostic impact evaluation, functional enrichment analysis, drug target annotation, tumor stratification and independent validation. Some pathways including the dynactin, cohesion and pyruvate dehydrogenase-related subnetworks are identified as promising new targets for therapy in specific cancer types. In conclusion, this integrative analysis of existing protein interactome and cancer genomics data allows us to systematically dissect the molecular mechanisms that underlie unexpected outcomes for cancer, which could be used to better understand and predict clinical outcomes, optimize treatment and to provide new opportunities for developing therapeutics related to the subnetworks identified.

  16. Increased expression of TRPS1 affects tumor progression and correlates with patients' prognosis of colon cancer.

    PubMed

    Hong, Jun; Sun, Jie; Huang, Tao

    2013-01-01

    To detect the expression pattern of tricho-rhino-phalangeal syndrome-1 (TRPS1) in human colon cancer and to analyze its correlation with prognosis of patients with this disease. The expressions of TRPS1 in human colon cancer and its corresponding noncancerous colon tissues were detected at both mRNA and protein levels. The mRNA and protein expression levels of TRPS1 were both significantly higher in colon cancer than in corresponding noncancerous colon tissues (both P < 0.001). The protein level of TRPS1 in colon cancer tissues was significantly correlated with the mRNA level (r = 0.9, P < 0.001). Additionally, immunohistochemistry analysis also found increased TRPS1 expression in 63.0% (63/100) of colon cancer tissues. High TRPS1 expression was significantly associated with positive lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.008) of patients with colon cancer. Multivariate Cox regression analysis further suggested that the increased expression of TRPS1 was an independent poor prognostic factor for this disease. Our data offer the convincing evidence for the first time that the increased expression of TRPS1 may be involved in the pathogenesis and progression of colon cancer. TRPS1 might be a potential marker to predict the prognosis in colon cancer.

  17. [Locally advanced prostate cancer: definition, prognosis and treatment].

    PubMed

    Plantade, Anne; Massard, Christophe; de Crevoisier, Renaud; Fizazi, Karim

    2007-07-01

    According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still

  18. Abnormal amphiregulin expression correlates with gastric cancer prognosis

    PubMed Central

    Wang, Bing; Yong, Hongmei; Zhu, Huijun; Ni, Daguang; Tang, Sijie; Zhang, Shu; Wang, Wei; Zhou, Yan; Zhao, Wei; Ding, Guipeng; Zhu, Jin; Li, Xiaohua; Feng, Zhenqing

    2016-01-01

    Gastric cancer (GC) is a global health issue with a high mortality rate. Early diagnosis and tracking of GC is a challenge due to a lack of reliable tools. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family that activates growth signaling upon binding of EGF receptors. Elevated AREG expression is associated with various pathological conditions, including cancer. Here, we investigated whether increased AREG expression is a disease indicator and/or prognostic biomarker for GC. We used tissue microarray and quantitative real-time polymerase chain reaction to assess AREG expression in clinical tissue specimens at various stages of GC and a conducted bioinformatics analysis to evaluate the value of AREG over-expression as a GC biomarker. We found that both mRNA and protein expression of AREG were increased in the tissues of GC patients when compared to tissues from non-cancer patients or normal tissues. High expression of AREG was also associated with GC clinicopathological characteristics and poor survival. Thus, over-expression of AREG could serve as a novel GC biomarker, and active surveillance of its expression could be a novel approach to GC diagnosis and monitoring. PMID:27713123

  19. Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

    PubMed Central

    Mihmanlı, Mehmet; Kabul Gürbulak, Esin; Akgün, İsmail Ethem; Celayir, Mustafa Fevzi; Yazıcı, Pınar; Tunçel, Deniz; Bek, Tuba Tülin; Öz, Ayhan; Ömeroğlu, Sinan

    2016-01-01

    AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response. PMID:27672428

  20. High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

    PubMed Central

    Liu, Ying; Zhang, Yu; Zhao, Ying; Gao, Dongna; Xing, Jing; Liu, Hui

    2016-01-01

    Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously demonstrated to be overexpressed in numerous malignant tumors and associated with invasiveness and poor prognosis. However, the expression of the PARP-1 protein in gastric cancer and its association with clinical outcomes requires further investigation. In the present study, the expression of PARP-1 in 564 gastric cancer tissues and 335 tumor-adjacent control tissues is investigated, using tissue microarray-based immunohistochemistry. PARP-1 expression levels were demonstrated to be significantly higher in gastric cancer tissue samples, as compared with control tissue samples. In gastric cancer, high PARP-1 expression levels were significantly associated with Helicobacter pylori (H. pylori) infection (P=0.032), decreased differentiation (P<0.001), increased depth of invasion (P=0.037), presence of lymphatic invasion (P<0.001), presence of lymph node metastasis (P<0.001), and advanced tumor-node-metastasis (TNM) stage (P=0.015). High PARP-1 expression levels were associated with a significantly shorter overall survival rate (P<0.001) and disease-free survival rate (P=0.001) in patients with gastric cancer, particularly a subset of patients with H. pylori infection or an advanced TNM stage. In addition, univariate analysis indicated that PARP-1 high expression levels were significantly associated with a poor prognosis in gastric cancer. These results suggest that PARP-1 expression may be involved in the progression and prognosis of gastric cancer, particularly H. pylori-positive or advanced-stage gastric cancer. PMID:27895737

  1. Exploring new quantitative CT image features to improve assessment of lung cancer prognosis

    NASA Astrophysics Data System (ADS)

    Emaminejad, Nastaran; Qian, Wei; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2015-03-01

    Due to the promotion of lung cancer screening, more Stage I non-small-cell lung cancers (NSCLC) are currently detected, which usually have favorable prognosis. However, a high percentage of the patients have cancer recurrence after surgery, which reduces overall survival rate. To achieve optimal efficacy of treating and managing Stage I NSCLC patients, it is important to develop more accurate and reliable biomarkers or tools to predict cancer prognosis. The purpose of this study is to investigate a new quantitative image analysis method to predict the risk of lung cancer recurrence of Stage I NSCLC patients after the lung cancer surgery using the conventional chest computed tomography (CT) images and compare the prediction result with a popular genetic biomarker namely, protein expression of the excision repair cross-complementing 1 (ERCC1) genes. In this study, we developed and tested a new computer-aided detection (CAD) scheme to segment lung tumors and initially compute 35 tumor-related morphologic and texture features from CT images. By applying a machine learning based feature selection method, we identified a set of 8 effective and non-redundant image features. Using these features we trained a naïve Bayesian network based classifier to predict the risk of cancer recurrence. When applying to a test dataset with 79 Stage I NSCLC cases, the computed areas under ROC curves were 0.77±0.06 and 0.63±0.07 when using the quantitative image based classifier and ERCC1, respectively. The study results demonstrated the feasibility of improving accuracy of predicting cancer prognosis or recurrence risk using a CAD-based quantitative image analysis method.

  2. p16 upregulation is linked to poor prognosis in ERG negative prostate cancer.

    PubMed

    Burdelski, Christoph; Dieckmann, Tatsiana; Heumann, Asmus; Hube-Magg, Claudia; Kluth, Martina; Beyer, Burkhard; Steuber, Thomas; Pompe, Raisa; Graefen, Markus; Simon, Ronald; Minner, Sarah; Tsourlakis, Maria Christina; Koop, Christina; Izbicki, Jakob; Sauter, Guido; Krech, Till; Schlomm, Thorsten; Wilczak, Waldemar; Lebok, Patrick

    2016-09-01

    Altered expression of the p16 tumor suppressor is frequently found in prostate cancer, but its role for tumor development and patient prognosis is disputed. In order to clarify the prognostic role of p16 and to draw conclusions on interactions with key molecular features of prostate cancer, we studied p16 expression in a tissue microarray (TMA) with more than 12,400 prostate cancers and attached clinical, pathological, and molecular data such as ERG status and deletions of 3p13, 5q21, 6q15, and PTEN. p16 immunostaining was absent in non-neoplastic prostate cells but was found in 37 % of 9627 interpretable prostate cancers. Finding p16 expression in 58 % of ERG positive but in only 22 % of ERG negative cancers (p < 0.0001), highlights the known androgen-dependence of both genes. Significant associations between p16 upregulation and tumor phenotype or patient prognosis were strictly limited to the subset of ERG negative cancers. For example, p16 positivity increased from 15 % in Gleason ≤3 + 3 to 38 % in Gleason ≥4 + 4 cancers (p < 0.0001) and was associated with early PSA recurrence (p < 0.0001). p16 upregulation was strongly linked to deletions of PTEN (p < 0.0001), highlighting the interaction of both genes in growth control. In conclusion, p16 upregulation is a strong prognostic factor in ERG negative cancers. The strict limitation of its prognostic impact to a molecularly defined subgroup challenges the concept of molecular prognosis testing without considering molecular subtypes.

  3. Colon cancer: diagnosis and prognosis in the elderly.

    PubMed

    Block, G E

    1989-05-01

    Cancer of the colon and rectum appear to be epidemic in the US, with 150,000 cases expected during 1988. Two thirds of these patients are over age 60, and two thirds also have either full penetration of the bowel wall or metastases to regional lymph nodes. Mass screening via tests for occult blood in the stool is invaluable for detecting early carcinomas of the colon and rectum. Digital examination, endoscopy, and barium contrast radiographs help to confirm the diagnosis. Tumors of the colon and rectum are best treated operatively with appropriate lymphadenectomy and adequate margins, both proximally and distally, to guard against local recurrence. Certain factors, such as mucinous tumors, microinvasion, and non-exophytic tumors of the rectum have been shown to have a propensity for local recurrence. Local treatment by fulguration or electrocoagulation is advocated only for tiny tumors confined to a polyp, or for the extremely elderly or poor-risk patient. Radiation therapy appears to be an appropriate adjuvant to the treatment of rectal cancer either preoperatively or postoperatively.

  4. The application of data mining techniques to oral cancer prognosis.

    PubMed

    Tseng, Wan-Ting; Chiang, Wei-Fan; Liu, Shyun-Yeu; Roan, Jinsheng; Lin, Chun-Nan

    2015-05-01

    This study adopted an integrated procedure that combines the clustering and classification features of data mining technology to determine the differences between the symptoms shown in past cases where patients died from or survived oral cancer. Two data mining tools, namely decision tree and artificial neural network, were used to analyze the historical cases of oral cancer, and their performance was compared with that of logistic regression, the popular statistical analysis tool. Both decision tree and artificial neural network models showed superiority to the traditional statistical model. However, as to clinician, the trees created by the decision tree models are relatively easier to interpret compared to that of the artificial neural network models. Cluster analysis also discovers that those stage 4 patients whose also possess the following four characteristics are having an extremely low survival rate: pN is N2b, level of RLNM is level I-III, AJCC-T is T4, and cells mutate situation (G) is moderate.

  5. Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer

    PubMed Central

    Arner, Peter; Henjes, Frauke; Schwenk, Jochen M.; Darmanis, Spyros; Dahlman, Ingrid; Iresjö, Britt-Marie; Naredi, Peter; Agustsson, Thorhallur; Lundholm, Kent; Nilsson, Peter; Rydén, Mikael

    2015-01-01

    Background Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC. PMID:25898255

  6. MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis

    PubMed Central

    Terunuma, Atsushi; Putluri, Nagireddy; Mishra, Prachi; Mathé, Ewy A.; Dorsey, Tiffany H.; Yi, Ming; Wallace, Tiffany A.; Issaq, Haleem J.; Zhou, Ming; Killian, J. Keith; Stevenson, Holly S.; Karoly, Edward D.; Chan, King; Samanta, Susmita; Prieto, DaRue; Hsu, Tiffany Y.T.; Kurley, Sarah J.; Putluri, Vasanta; Sonavane, Rajni; Edelman, Daniel C.; Wulff, Jacob; Starks, Adrienne M.; Yang, Yinmeng; Kittles, Rick A.; Yfantis, Harry G.; Lee, Dong H.; Ioffe, Olga B.; Schiff, Rachel; Stephens, Robert M.; Meltzer, Paul S.; Veenstra, Timothy D.; Westbrook, Thomas F.; Sreekumar, Arun; Ambs, Stefan

    2013-01-01

    Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher frequency in African-American patients. Tumors of this subtype had a stem cell–like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis. PMID:24316975

  7. Comparison of percutaneous microwave ablation and laparoscopic resection in the prognosis of liver cancer.

    PubMed

    Xu, Juan; Zhao, Ye

    2015-01-01

    The effect of percutaneous microwave ablation and laparoscopic resection on the prognosis of liver cancer was investigated. Ninety patients with liver cancer treated at our hospital from March 2010 to March 2012 were divided into group A and group B (n=45) by using a random number table, and the surgical conditions and the prognosis were compared. The surgical conditions of patients in group A were significantly better than those in group B (P<0.05). The incidence of complications in group A was 6.67%, which was obviously lower than that of group B (P<0.05). The local recurrence rate of group A was 20.00%, and that of group B was 8.89%, which showed a significant difference (P<0.05). The two groups did not differ significantly in terms of either total recurrence rate (P>0.05) or 1-year, 2-year and 3-year survival (P>0.05). Both percutaneous microwave ablation and laparoscopic resection had a good long-term efficacy in liver cancer. However, percutaneous microwave ablation was superior as it caused less invasiveness, reduced the incidence of complications and improved prognosis of liver cancer.

  8. Cytological nuclear atypia classification can predict prognosis in patients with endometrial cancer.

    PubMed

    Yamaguchi, T; Kawahara, A; Hattori, S; Taira, T; Abe, H; Sanada, S; Akiba, J; Nishio, S; Ushijima, K; Kamura, T; Kage, M

    2015-06-01

    Endometrial cancer is one of the leading causes of malignancy in females. Nuclear findings are important for patients with cancer, and can provide valuable information to treating oncologists. We investigated whether nuclear findings were a useful prognostic factor in patients with endometrial cancer. We investigated 71 cases of endometrial carcinoma with paired histology and cytology at Kurume University Hospital. We classified endometrial endometrioid adenocarcinoma (EEC) G1 and G2 as type I carcinomas, and uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC) and EEC G3 as type II carcinomas. For the establishment of the cytological nuclear atypia classification, we examined the following nuclear factors on the cytological smears: mitotic figures, prominent nucleoli, nuclear area and anisonucleosis. There was a significant difference in mitotic figures (P < 0.001) and anisonucleosis (P = 0.026) in cytological smears between type I and type II carcinomas. Based on these findings, we categorized cytological nuclear atypia into three groups, nuclear atypia-1 (57.7%), nuclear atypia-2 (19.7%) and nuclear atypia-3 (22.5%), and this classification system correlated well with prognosis in patients with endometrial cancer (P < 0.001). Furthermore, this classification system was able to extract patients with a good prognosis from those with high-grade carcinomas, such as UPSC+CC+EEC G3, and patients with a poor prognosis from those with EEC G1. Our system of cytological nuclear atypia classification based on endometrial cytology can predict patient prognosis. Cytological nuclear atypia classification and histological typing may be useful for the treatment and follow-up of patients with endometrial cancer, and should be routinely incorporated into cytological reports. © 2014 John Wiley & Sons Ltd.

  9. Characteristics and prognosis of breast cancer after liver or kidney transplantation.

    PubMed

    Jeong, I-Ji; Lee, Sung-Gyu; Kim, Young Hoon; Ko, Beom Seok; Lee, Jong Won; Son, Byung Ho; Ahn, Se-Hyun; Kim, Hee Jeong

    2017-09-15

    Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. After a median of 61 and 90.8 months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p = 0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2 ± 4.5 vs. 48.5 ± 10.1 years; p = 0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p = 0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p = 0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p = 0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.

  10. Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer

    NASA Astrophysics Data System (ADS)

    Zhang, Yucheng; Oikonomou, Anastasia; Wong, Alexander; Haider, Masoom A.; Khalvati, Farzad

    2017-04-01

    Radiomics characterizes tumor phenotypes by extracting large numbers of quantitative features from radiological images. Radiomic features have been shown to provide prognostic value in predicting clinical outcomes in several studies. However, several challenges including feature redundancy, unbalanced data, and small sample sizes have led to relatively low predictive accuracy. In this study, we explore different strategies for overcoming these challenges and improving predictive performance of radiomics-based prognosis for non-small cell lung cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who underwent stereotactic body radiotherapy were used to predict recurrence, death, and recurrence-free survival using a comprehensive radiomics analysis. Different feature selection and predictive modeling techniques were used to determine the optimal configuration of prognosis analysis. To address feature redundancy, comprehensive analysis indicated that Random Forest models and Principal Component Analysis were optimum predictive modeling and feature selection methods, respectively, for achieving high prognosis performance. To address unbalanced data, Synthetic Minority Over-sampling technique was found to significantly increase predictive accuracy. A full analysis of variance showed that data endpoints, feature selection techniques, and classifiers were significant factors in affecting predictive accuracy, suggesting that these factors must be investigated when building radiomics-based predictive models for cancer prognosis.

  11. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis.

    PubMed

    Bradbury, Penelope A; Zhai, Rihong; Ma, Clement; Xu, Wei; Hopkins, Jessica; Kulke, Matthew J; Asomaning, Kofi; Wang, Zhaoxi; Su, Li; Heist, Rebecca S; Lynch, Thomas J; Wain, John C; Christiani, David; Liu, Geoffrey

    2009-07-15

    Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The VEGF gene is polymorphic. We investigated the prognostic significance of three VEGF single nucleotide polymorphisms (SNP) in esophageal cancer. Three hundred sixty-one patients were genotyped for three VEGF SNPs (-460T/C, 405G/C, and 936C/T) using DNA extracted from prospectively collected blood samples. The association of each individual SNP, and haplotypes of the three SNPs, on overall survival (OS) was investigated. The variant allele of 936C/T was associated with improved OS compared with the wild-type genotype (log-rank P < 0.001). This association remained significant for OS after adjustments for age, gender, performance status, and disease stage [VEGF 936C/T: adjusted hazard ratio (AHR), 0.70; 95% confidence interval (95% CI), 0.49-0.99; P = 0.04; VEGF 936T/T: AHR, 0.11; 95% CI, 0.02-0.82; P = 0.03]. No independent associations were found for VEGF -460T/C and VEGF 405G/C. The CGC haplotype of the three VEGF SNPs (-460T/C, 405G/C, and 936C/T) combined was associated with reduced OS compared with all other patients (CGC/CGC: AHR, 1.51; 95% CI, 1.00-2.30; P = 0.05). VEGF 936C/T, and a haplotype of 460T/C, 405G/C, and 936C/T combined, has potential prognostic significance in esophageal cancer.

  12. Up-regulation of Tim-3 is associated with poor prognosis of patients with colon cancer.

    PubMed

    Zhou, Encheng; Huang, Qing; Wang, Ji; Fang, Chengfeng; Yang, Leilei; Zhu, Min; Chen, Jianhui; Chen, Lihua; Dong, Milian

    2015-01-01

    Tim-3 (T cell immunoglobulin and mucin domain 3), belonging to the member of the novel Tim family, has been confirmed that it plays a critical negative role in regulating the immune responses against viral infection and carcinoma. Recently, it has also been reported that the over-expression of Tim-3 is associated with poor prognosis in solid tumors. However, the role of Tim-3 in colorectal cancer remains largely unknown. In the current study, we aim to investigate the expression of Tim-3 in colorectal carcinoma and discuss the relationship between Tim-3 expression and colon cancer prognosis, thus speculating the possible role of Tim-3 in colon cancer progression. Colon cancer tissues and paired normal tissue were obtained from 201 patients with colon cancer for preparation of tissue microarray. Tim-3 expression was evaluated by immunohistochemical staining. The Tim-3 expression level was evaluated by q-RT-PCR, western blot and immunocytochemistry in four colon cancer cell lines (HT-29, HCT116, LoVo, SW620). Tim-3 was expressed in 92.5% tumor tissue samples and 86.5% corresponding normal tissue samples. Expression of Tim-3 was significantly higher in tumor tissues than in normal tissues (P < 0.0001). Tim-3 expression in colon cancer tissues is in correlation with colon cancer lymphatic metastasis and TNM (P < 0.0001). Multivariate analysis demonstrated that Tim-3 expression could be a potential independent prognostic factor for colon cancer patients (P < 0.0001). Kaplan-Meier survival analysis result showed that patients with higher Tim-3 expression had a significantly shorter survival time than those with lower Tim-3 expression patients. Our results indicated that Tim-3 might participate in the tumorgenesis of colon cancer and Tim-3 expression might be a potential independent prognostic factor for patients with colorectal cancer.

  13. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis.

    PubMed

    Zhang, Junjie; Zhang, Lijian; Ye, Xiaoxia; Chen, Liyu; Zhang, Liangtao; Gao, Yihua; Kang, Jing X; Cai, Chun

    2013-05-01

    To investigate tissue fatty acid distribution in relation to the incidence of colorectal cancer prognosis, adjacent normal tissue and cancerous tissue from 35 samples of clinically incident colorectal cancer were obtained. Fatty acids were measured in the colorectal mucosa phospholipid fraction by gas chromatography mass spectrometry. Palmitoleic acid and oleic acid were significantly lower in colorectal cancerous tissue, ranging from 20% to 50% less than the adjacent normal tissue. The omega-6 (n-6) fatty acid family members (20:2, 20:3, 20:4 and 22:4) were higher by 1-3 fold in cancerous colorectal tissue. Contrary with the high level of n-6 fatty acids, about a 37% to 87% reduction in EPA and DHA was observed in colorectal cancerous tissue. A higher level of linoleic acid and arachidonic acid was detected in the C cancer stage than in the B cancer stage (p<0.05), but a lower level of oleic acid and docosahexenoic acid was detected in the C cancer stage (p<0.05). The fatty acid distribution of colorectal tissue is strongly linked to the incidence of colorectal cancer. This study also provides scientific basis for identifying novel biomarkers for the diagnosis and treatment of cancer.

  14. Four microRNAs Signature for Survival Prognosis in Colon Cancer using TCGA Data

    PubMed Central

    Xu, Jian; Zhao, Jian; Zhang, Rui

    2016-01-01

    This study aims to develop microRNA expression signature for colon cancer survival prognosis based on the Cancer Genomic Common database. miRNAs levels between colon cancer and non-cancer tissues were screened by t-test (p < 0.05). Kaplan-Meier survival method was used to discriminate survival significant miRNAs, followed by miRNAs index accumulation to power the miRNAs-survival reliability. In the end, we test the selected miRNAs in HT126 colon cancer cells to validate its anti-cancer effect. The study identified a 84-miRNAs signature. Of the above 84 miRNAs, we got four miRNAs which were survival associated by using ROC curve method and Kaplan-Meier survival method (p < 0.001). The result showed that low risk group had quite a low death rate, the survival rate was over 80%. The high risk group had survival rate lower than 20%, which was also extremely lower than the overall survival rate. In the HT126 cells study, cell growth assay showed miR-130a sponge inhibited colon cancer cells growth and sensitized the anti-cancer drug effect of 5-FU to blocked cancer cell growth. We developed a prognostic 4-microRNA expression signature for colon cancer patient survival, and validated miR-130a sponge could sensitized 5-FU anti-cancer effect. PMID:27974852

  15. C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management.

    PubMed

    Thirunavukarasu, Pragatheeshwar; Sukumar, Shyamsunder; Sathaiah, Magesh; Mahan, Meredith; Pragatheeshwar, Kothai Divya; Pingpank, James F; Zeh, Herbert; Bartels, Christopher J; Lee, Kenneth K W; Bartlett, David L

    2011-04-20

    The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

  16. Circulating Tumor Cells in Breast Cancer Patients: An Evolving Role in Patient Prognosis and Disease Progression

    PubMed Central

    Graves, Holly; Czerniecki, Brian J.

    2011-01-01

    In this paper, we examine the role of circulating tumor cells (CTCs) in breast cancer. CTCs are tumor cells present in the peripheral blood. They are found in many different carcinomas but are not present in patients with benign disease. Recent advances in theories regarding metastasis support the role of early release of tumor cells in the neoplastic process. Furthermore, it has been found that phenotypic variation exists between the primary tumor and CTCs. Of particular interest is the incongruency found between primary tumor and CTC HER2 status in both metastatic and early breast cancer. Overall, CTCs have been shown to be a poor prognostic marker in metastatic breast cancer. CTCs in early breast cancer are not as well studied, however, several studies suggest that the presence of CTCs in early breast cancer may also suggest a poorer prognosis. Studies are currently underway looking at the use of CTC level monitoring in order to guide changes in therapy. PMID:21253472

  17. High copy number of mitochondrial DNA predicts poor prognosis in patients with advanced stage colon cancer.

    PubMed

    Wang, Yun; He, Shuixiang; Zhu, Xingmei; Qiao, Wei; Zhang, Juan

    2016-12-23

    The aim of this investigation was to determine whether alterations in mitochondrial DNA (mtDNA) copy number in colon cancer were associated with clinicopathological parameters and postsurgical outcome. By quantitative real-time PCR assay, the mtDNA copy number was detected in a cohort of colon cancer and matched adjacent colon tissues (n = 162). The majority of patients had higher mtDNA content in colon cancer tissues than matched adjacent colon tissues. Moreover, high mtDNA content in tumor tissues was associated with larger tumor size, higher serum CEA level, advanced TNM stage, vascular emboli, and liver metastases. Further survival curve analysis showed that high mtDNA content was related to the worst survival in patients with colon cancer at advanced TNM stage. High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer.

  18. Prognosis and treatment of patients with positive peritoneal cytology in advanced gastric cancer

    PubMed Central

    Frattini, Francesco; Rausei, Stefano; Chiappa, Corrado; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2013-01-01

    Positive peritoneal cytology in gastric cancer is classified as M1 disease by the 7th Edition of American Joint Committee on Cancer staging system. With the introduction of laparoscopy and peritoneal washing cytology in the staging of gastric cancer a new category of patients has been identified. These are patients with no macroscopic peritoneal metastases but with peritoneal cytology positive (P0C1). Prognosis and treatment of such patients represent a controversial issue. We evaluate the state of the art of staging system in gastric cancer and discuss standardisation in staging and treatment procedures. There is still a lack of uniformity in the use of laparoscopy with peritoneal cytology in clinical decision making and in the surgical treatment for gastric cancer. Survival of this patient subset remains poor. Multimodal therapies and new therapeutic strategies are required to improve the survival of these patients. PMID:23710290

  19. Prognosis and treatment of patients with positive peritoneal cytology in advanced gastric cancer.

    PubMed

    Frattini, Francesco; Rausei, Stefano; Chiappa, Corrado; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2013-05-27

    Positive peritoneal cytology in gastric cancer is classified as M1 disease by the 7(th) Edition of American Joint Committee on Cancer staging system. With the introduction of laparoscopy and peritoneal washing cytology in the staging of gastric cancer a new category of patients has been identified. These are patients with no macroscopic peritoneal metastases but with peritoneal cytology positive (P0C1). Prognosis and treatment of such patients represent a controversial issue. We evaluate the state of the art of staging system in gastric cancer and discuss standardisation in staging and treatment procedures. There is still a lack of uniformity in the use of laparoscopy with peritoneal cytology in clinical decision making and in the surgical treatment for gastric cancer. Survival of this patient subset remains poor. Multimodal therapies and new therapeutic strategies are required to improve the survival of these patients.

  20. [Use of micro RNAs in the diagnosis and prognosis of colorectal cancer (CCR)].

    PubMed

    Arredondo-Valdez, Abril Reneé; Wence-Chavez, Laura; Rosales-Reynoso, Mónica Alejandra

    2016-01-01

    The aim of this review is to present a general overview about the importance of micro RNAs (miRNAs) in colorectal carcinoma. First, we focused on the mechanisms whereby the miRNAs regulate the expression of target genes, and how an altered regulation of them is associated with several types of cancer, including colorectal carcinoma. Later, examples of some miRNAs that have been associated with cancer development and how the expression patterns of specific miRNAs can be used as potential biomarkers for prognosis, diagnosis and therapeutic outcome in colorectal carcinoma are addressed. Finally, several polymorphisms presents in the miRNAs that have been associated to risk and prognosis in colorectal carcinoma are described.

  1. Implications of microRNAs in colorectal cancer development, diagnosis, prognosis, and therapeutics.

    PubMed

    Zhai, Haiyan; Ju, Jingfang

    2011-11-03

    MicroRNAs (miRNAs) are a class of non-coding small RNAs with critical regulatory functions as post-transcriptional regulators. Due to the fundamental importance and broad impact of miRNAs on multiple genes and pathways, dysregulated miRNAs have been associated with human diseases, including cancer. Colorectal cancer (CRC) is among the most deadly diseases, and miRNAs offer a new frontier for target discovery and novel biomarkers for both diagnosis and prognosis. In this review, we summarize the recent advancement of miRNA research in CRC, in particular, the roles of miRNAs in CRC stem cells, epithelial-to-mesenchymal transition, chemoresistance, therapeutics, diagnosis, and prognosis.

  2. Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer.

    PubMed

    Zhang, Yiqian; Jiang, Chunling; Li, Huilan; Lv, Feng; Li, Xiaoyan; Qian, Xiaolong; Fu, Li; Xu, Bo; Guo, Xiaojing

    2015-01-01

    Aurora-B is a major kinase responsible for appropriate mitotic progression. Elevated expression of Aurora-B has been frequently associated with several types of cancer, including breast cancer. However, it is not clear whether the alteration contributes to tumor responses to therapies and prognosis. In this study, we conducted immunohistochemistry using antibodies against Aurora-B, S1981p-ATM, Ki67, and p53 in paraffin-embedded tumor tissues from 312 invasive breast cancer patients. The correlation between disease-free-survival (DFS) and Aurora-B expression was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards regression analysis was used to determine whether Aurora-B was an independent prognostic factor for breast cancer. We found that Aurora-B expression was correlated with the proliferation index (P < 0.001) and p53 expression (P = 0.014) in breast cancer tissues. Further we found that Aurora-B expression was associated with lymph node metastasis (P = 0.002) and histological grade (P = 0.001). Multivariate analyses indicated that elevated Aurora-B expression predicted a poor survival. In a subgroup of patients that received neoadjuvant chemotherapy, we found that elevated Aurora-B contributed to chemoresistance (P = 0.011). In conclusion, elevated Aurora-B expression in breast cancer patients contributes to chemoresistance and predicts poor prognosis.

  3. Correlation of NGX6 expression with clinicopathologic features and prognosis in colon cancer.

    PubMed

    Xiao, Jidong; Zhou, Yuanquan; Liu, Bo

    2015-01-01

    The aim was to explore the correlation of NGX6 expression with clinicopathological features and prognosis in colon cancer. Clinicopathological feature of 145 patients with colon cancer were analyzed.NGX6 expression was measured using immunohistochemistry methods. The correlation of NGX6 expression with clinicopathological features and prognosis were assessed. Among 145 cases of colon cancer, NGX6 positive expression were found in 76 (52.4%) cases and NGX6 negative expression were found in 69 (47.6%) cases. The expression of NGX6 was closely associated with size tumor, lymph node metastasis and TNM stage (P=0.002, 0.012, and 0.039, respectively). Kaplan-Meier analysis showed that NGX6 negative expression was associated with shorter disease-free survival (DFS) (P=0.029) and overall survival (OS) (P=0.015). Multivariate survival analysis demonstrated that NGX6 expression was the important independent prognostic factor for colon cancer (P=0.022). NGX6 is involved in the invasion and metastasis activity of colon cancer. NGX6 could may be applied as a novel and promising prognostic marker for colon cancer.

  4. Can Molecular Biomarkers Change the Paradigm of Pancreatic Cancer Prognosis?

    PubMed Central

    Garcia-Foncillas, Jesus

    2016-01-01

    Pancreatic ductal adenocarcinoma is one of the most lethal types of tumour, and its incidence is rising worldwide. Although survival can be improved when these tumours are detected at an early stage, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. The only prognostic biomarker approved by the FDA to date is carbohydrate antigen 19-9 (CA19-9); however, the specificity of this biomarker has been called into question, and diagnosis is usually based on clinical parameters. Tumour size, degree of differentiation, lymph node status, presence of distant metastasis at diagnosis, protein levels of KI-67 or C-reactive protein, and mutational status of P53, KRAS, or BRCA2 are the most useful biomarkers in clinical practice. In addition to these, recent translational research has provided evidence of new biomarkers based on different molecules involved in endoplasmic reticulum stress, epithelial-to-mesenchymal transition, and noncoding RNA panels, especially microRNAs and long noncoding RNAs. These new prospects open new paths to tumour detection using minimally or noninvasive techniques such as liquid biopsies. To find sensitive and specific biomarkers to manage these patients constitutes a challenge for the research community and for public health policies. PMID:27689078

  5. Identification of inherited genetic variations influencing prognosis in early-onset breast cancer.

    PubMed

    Rafiq, Sajjad; Tapper, William; Collins, Andrew; Khan, Sofia; Politopoulos, Ioannis; Gerty, Sue; Blomqvist, Carl; Couch, Fergus J; Nevanlinna, Heli; Liu, Jianjun; Eccles, Diana

    2013-03-15

    Genome-Wide Association Studies (GWAS) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here, we report our findings from a GWAS conducted in 536 patients with early-onset breast cancer aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (SD = 1.96). Patients were selected from the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer. A Bonferroni correction for multiple testing determined that a P value of 1.0 × 10(-7) was a statistically significant association signal. Following quality control, we identified 487,496 single nucleotide polymorphisms (SNP) for association tests in stage 1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1,516 independent cases from the same early-onset cohort. In stage 2, 11 SNPs remained associated in the same direction (P ≤ 0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus [HR = 1.61; 95% confidence interval (CI), 1.33-1.96; P = 9.5 × 10(-7)]. Four further associations at or close to the PBX1, RORα, NTN1, and SYT6 loci also came close to genome-wide significance levels (P = 10(-6)). In the first ever GWAS for the identification of SNPs associated with prognosis in patients with early-onset breast cancer, we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (median follow-up time for genotypes: CC = 4 years, CT = 3 years, and TT = 2.7 years; Wilcoxon rank-sum test CC vs. CT, P = 4 × 10(-4) and CT vs. TT, P = 0.76). Four further loci may also be associated with prognosis.

  6. Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer

    PubMed Central

    Jorissen, Robert N; Christie, Michael; Mouradov, Dmitri; Sakthianandeswaren, Anuratha; Li, Shan; Love, Christopher; Xu, Zheng-Zhou; Molloy, Peter L; Jones, Ian T; McLaughlin, Stephen; Ward, Robyn L; Hawkins, Nicholas J; Ruszkiewicz, Andrew R; Moore, James; Burgess, Antony W; Busam, Dana; Zhao, Qi; Strausberg, Robert L; Lipton, Lara; Desai, Jayesh; Gibbs, Peter; Sieber, Oliver M

    2015-01-01

    Background: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. Methods: APC prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. Results: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). Conclusions: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer. PMID:26305864

  7. Incorporating higher-order representative features improves prediction in network-based cancer prognosis analysis.

    PubMed

    Ma, Shuangge; Kosorok, Michael R; Huang, Jian; Dai, Ying

    2011-01-12

    In cancer prognosis studies with gene expression measurements, an important goal is to construct gene signatures with predictive power. In this study, we describe the coordination among genes using the weighted coexpression network, where nodes represent genes and nodes are connected if the corresponding genes have similar expression patterns across samples. There are subsets of nodes, called modules, that are tightly connected to each other. In several published studies, it has been suggested that the first principal components of individual modules, also referred to as "eigengenes", may sufficiently represent the corresponding modules. In this article, we refer to principal components and their functions as representative features". We investigate higher-order representative features, which include the principal components other than the first ones and second order terms (quadratics and interactions). Two gradient thresholding methods are adopted for regularized estimation and feature selection. Analysis of six prognosis studies on lymphoma and breast cancer shows that incorporating higher-order representative features improves prediction performance over using eigengenes only. Simulation study further shows that prediction performance can be less satisfactory if the representative feature set is not properly chosen. This study introduces multiple ways of defining the representative features and effective thresholding regularized estimation approaches. It provides convincing evidence that the higher-order representative features may have important implications for the prediction of cancer prognosis.

  8. Incorporating higher-order representative features improves prediction in network-based cancer prognosis analysis

    PubMed Central

    2011-01-01

    Background In cancer prognosis studies with gene expression measurements, an important goal is to construct gene signatures with predictive power. In this study, we describe the coordination among genes using the weighted coexpression network, where nodes represent genes and nodes are connected if the corresponding genes have similar expression patterns across samples. There are subsets of nodes, called modules, that are tightly connected to each other. In several published studies, it has been suggested that the first principal components of individual modules, also referred to as "eigengenes", may sufficiently represent the corresponding modules. Results In this article, we refer to principal components and their functions as representative features". We investigate higher-order representative features, which include the principal components other than the first ones and second order terms (quadratics and interactions). Two gradient thresholding methods are adopted for regularized estimation and feature selection. Analysis of six prognosis studies on lymphoma and breast cancer shows that incorporating higher-order representative features improves prediction performance over using eigengenes only. Simulation study further shows that prediction performance can be less satisfactory if the representative feature set is not properly chosen. Conclusions This study introduces multiple ways of defining the representative features and effective thresholding regularized estimation approaches. It provides convincing evidence that the higher-order representative features may have important implications for the prediction of cancer prognosis. PMID:21226928

  9. Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype.

    PubMed

    Sun, Xuezheng; Nichols, Hazel B; Tse, Chiu-Kit; Bell, Mary B; Robinson, Whitney R; Sherman, Mark E; Olshan, Andrew F; Troester, Melissa A

    2016-01-01

    Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis have received limited attention. Study participants were 1,140 invasive breast cancer patients from phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer-specific and overall survival was assessed using Cox proportional hazards models. During follow-up (median = 13.5 years), 450 patients died, 61% due to breast cancer (n = 276). High parity (3+ births) and recent birth (<5 years before diagnosis) were positively associated with breast cancer-specific mortality, independent of age, race, and selected socioeconomic factors [parity, reference = nulliparous, adjusted HR = 1.76; 95% confidence interval (CI) = 1.13-2.73; birth recency, reference = 10+ years, adjusted HR = 1.29; 95% CI, 0.79-2.11]. The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long-term survivors. The biologic effects of parity and birth recency may extend from etiology to tumor promotion and progression. ©2015 American Association for Cancer Research.

  10. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

    PubMed

    Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2015-03-30

    Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

  11. Guanine nucleotide binding protein-like 3 is a potential prognosis indicator of gastric cancer.

    PubMed

    Chen, Jing; Dong, Shuang; Hu, Jiangfeng; Duan, Bensong; Yao, Jian; Zhang, Ruiyun; Zhou, Hongmei; Sheng, Haihui; Gao, Hengjun; Li, Shunlong; Zhang, Xianwen

    2015-01-01

    Guanine nucleotide binding protein-like 3 (GNL3) is a GIP-binding nuclear protein that has been reported to be involved in various biological processes, including cell proliferation, cellular senescence and tumorigenesis. This study aimed to investigate the expression level of GNL3 in gastric cancer and to evaluate the relationship between its expression and clinical variables and overall survival of gastric cancer patients. The expression level of GNL3 was examined in 89 human gastric cancer samples using immunohistochemistry (IHC) staining. GNL3 in gastric cancer tissues was significantly upregulated compared with paracancerous tissues. GNL3 expression in adjacent non-cancerous tissues was associated with sex and tumor size. Survival analyses showed that GNL3 expression in both gastric cancer and adjacent non-cancerous tissues were not related to overall survival. However, in the subgroup of patients with larger tumor size (≥ 6 cm), a close association was found between GNL3 expression in gastric cancer tissues and overall survival. GNL3-positive patients had a shorter survival than GNL3-negative patients. Our study suggests that GNL3 might play an important role in the progression of gastric cancer and serve as a biomarker for poor prognosis in gastric cancer patients.

  12. [Influence of body weight on the prognosis of breast cancer survivors; nutritional approach after diagnosis].

    PubMed

    Rodríguez San Felipe, María Jesús; Aguilar Martínez, Alicia; Manuel-y-Keenoy, Begoña

    2013-11-01

    Obesity combined with breast cancer is a public health problem, given the high incidence and prevalence of both diseases. The aim of this review is to determine the current status of research on the relationship between the body weight of breast cancer patients and their prognosis. Overweight and obesity at the time of diagnosis are associated with a worse prognosis in breast cancer survivors. Observational studies show that breast cancer mortality is 33% higher in obese than in non-obese survivors. Furthermore, weight gain after diagnosis is common in these patients and is even greater in those receiving chemotherapy. Weight gains of 2-8 kg are observed in 68% of patients 3 years after diagnosis. Each 5 kg increase in body weight is associated with a 13% increase in breast cancer specific mortality. The mechanisms that cause this weight gain are not totally known. A higher weight gain is also associated with higher the risk of co-morbid cardiometabolic diseases, which worsen the quality of life and shorten overall survival. On the other hand, excess adipose tissue is an indirect promoter of tumor cell proliferation and releases circulating estrogens. Hence, preventing excess weight is important in these patients. An important limitation is the small number of randomised controlled trials investigating the type of diet that could be recommended specifically to breast cancer survivors. The evidence from current studies suggests that a healthy diet, low in fat and simple sugars and with a high proportion of fruit, vegetables and wholegrain products, has the potential to reduce morbidity and the risk of recurrence significantly, thus improving prognosis and quality of life in the long term.

  13. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer.

    PubMed

    Zhao, Yue; Dong, Xiaoqiu; Li, Rongguo; Ma, Xiao; Song, Jian; Li, Yingjie; Zhang, Dongwei

    2015-01-01

    The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer. A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG) and Residual Disease in Breast and Nodes (RDBN). Ten patients (11.4%) achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03). MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival. MPG and RDBN were similarly related to the patient's prognosis. MPG was more suitable for evaluation of distant disease-free survival, and RDBN was more suitable for evaluation of local recurrence-free survival. Survival following neoadjuvant chemotherapy correlated with the pathological reaction rather than the molecular subtype of breast cancer. The molecular subtype of breast cancer was not correlated with pathological response in patients who did not achieve a pathological complete response.

  14. [FACTORS OF PROGNOSIS IN PATIENTS WITH EARLY CANCER OF MAMMARY GLAND].

    PubMed

    Shchurov, M F; Voloshyna, N M; Pogorila, T Yu

    2015-12-01

    A survival indices in patients with early mammary gland cancer of a ductal infiltrating histology stage T1-2N0M0, who were treated in accordance to actual standards, differ significantly, what witnesses the necessity for searching of additional prognostic criteria. The investigation objective was to study the impact of independent and interrelated clinical, morphological and biochemical factors of prognosis on the survival indices in patients with mammary gland cancer stage T1-2N0M0 in conditions of local and systemic treatment.

  15. Breast cancer under 40 years of age: increasing number and worse prognosis.

    PubMed

    Dobi, Ágnes; Kelemen, Gyöngyi; Kaizer, László; Weiczner, Roland; Thurzó, László; Kahán, Zsuzsanna

    2011-06-01

    Breast cancer at a relatively young age with a poor prognosis is currently exhibiting an increasing incidence. In a retrospective cohort analysis of early breast cancer cases after surgery from our institutional patient registry, 141 patients aged ≤ 40 years constituted the younger group, with 300 randomly selected patients aged >40 years as controls. A significant and steady increase was found in the relative number of younger cases during the years 2004-2009. The histological type and grade and the lymph node status of the cancers differed significantly between the two groups, with more aggressive biological behaviour, a more advanced stage and a worse prognosis in the younger group. Half of the cancers in the younger cohort were ER-negative, while two-thirds in the control group were ER-positive. Comparatively more tumours were PR-positive and HER2-negative in the control group than in the younger group. The rates of triple-negative cases were 25% and 13% in the younger age and the control group, respectively (p = 0.026). Significantly higher mastectomy and axillary block dissection rates were observed in the younger age group, and more chemotherapy was administered than in the control group. Our findings demonstrate the significance of breast cancer in cases aged <40 years, and draw attention to the need for appropriate care in these cases.

  16. Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer.

    PubMed

    Murray, G I; Duncan, M E; O'Neil, P; McKay, J A; Melvin, W T; Fothergill, J E

    1998-07-01

    The matrix metalloproteinases (MMPs) are a family of closely related proteolytic enzymes which are involved in the degradation of different components of the extracellular matrix. There is increasing evidence to indicate that individual MMPs have an important role in tumour invasion and tumour spread. Monoclonal antibodies specific for MMP-1, MMP-2, or MMP-9 have been produced, using as immunogens peptides selected from the amino acid sequences of individual MMPs. The presence of MMP-1, MMP-2, and MMP-9 in oesophageal cancer was investigated by immunohistochemistry on formalin-fixed, wax-embedded sections of oesophageal cancers. The relationship of individual MMPs to prognosis and survival was determined. MMP-1 was present in 24 per cent of oesophageal cancers, while MMP-2 and MMP-9 were present in 78 and 70 per cent of tumours, respectively. The presence of MMP-1 was associated with a particularly poor prognosis (log rank test 8.46, P < 0.004) and was an independent prognostic factor (P = 0.02). The identification of individual MMPs in oesophageal cancer provides a rational basis for use in the treatment of oesophageal cancer of MMP inhibitors which are currently undergoing clinical trial.

  17. The cervical cancer prevention programme in Costa Rica.

    PubMed

    Rojas, Ileana Quirós

    2015-01-01

    Cervical and uterine cancer continues to be an important issue for women around the world, although neoplasia has the greatest demonstrated potential for prevention. Costa Rica has achieved important advances in the reduction of the incidence and mortality of these cancers since the last century. This is the result of a series of policies, programmes, and plans, not only at the level of the health care system, but also in other areas. Increased access for women to care in health centres, fundamentally at the primary level, has been vital, as has ensuring the quality of cytology readings and access to diagnosis and treatment for precursor lesions for in situ and invasive cancers. Despite all of these achievements, there are still challenges to be overcome, which are widespread in many countries in Latin America and the Caribbean. It is important to learn from the experiences of other countries in order to improve women's health not only as a health objective, but also as an ethical imperative to promote the exercise of women's rights to life and health.

  18. The cervical cancer prevention programme in Costa Rica

    PubMed Central

    Rojas, Ileana Quirós

    2015-01-01

    Cervical and uterine cancer continues to be an important issue for women around the world, although neoplasia has the greatest demonstrated potential for prevention. Costa Rica has achieved important advances in the reduction of the incidence and mortality of these cancers since the last century. This is the result of a series of policies, programmes, and plans, not only at the level of the health care system, but also in other areas. Increased access for women to care in health centres, fundamentally at the primary level, has been vital, as has ensuring the quality of cytology readings and access to diagnosis and treatment for precursor lesions for in situ and invasive cancers. Despite all of these achievements, there are still challenges to be overcome, which are widespread in many countries in Latin America and the Caribbean. It is important to learn from the experiences of other countries in order to improve women’s health not only as a health objective, but also as an ethical imperative to promote the exercise of women’s rights to life and health. PMID:26557876

  19. Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer.

    PubMed

    Liu, Shuli; Dong, Qianze; Wang, Enhua

    2012-10-01

    Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its biological roles in colon cancer have not been reported. The molecular mechanism of Rsf-1 in cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression pattern of Rsf-1 in colon cancer tissues and found that Rsf-1 was overexpressed in 50.4 % of colon cancer specimens. There was a significant association between Rsf-1 overexpression and TNM stage (p = 0.0205), lymph node metastasis (p = 0.0025), and poor differentiation (p = 0.0235). Furthermore, Rsf-1 overexpression correlated with a poor prognosis in colon cancer patients (p = 0.0011). In addition, knockdown of Rsf-1 expression in HT29 and HCT116 cells with high endogenous Rsf-1 expression decrease cell proliferation and colony formation ability. Further analysis showed that Rsf-1 knockdown decreased cyclin E expression and phospho-Rb level. In conclusion, Rsf-1 is overexpressed in colon cancers and contributes to malignant cell growth by cyclin E and phospho-Rb modulation, which makes Rsf-1 a candidate therapeutic target in colon cancer.

  20. Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer

    PubMed Central

    Oh, Tai Young; Shin, Ui Sup; Lee, Hyang Ran; Park, Sun Hoo

    2011-01-01

    Purpose Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. Methods The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. Results Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR ≤ 0.25 group was 92.9% (P = 0.03). Conclusion The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer. PMID:21602965

  1. Nutritional status, systemic inflammation and prognosis of patients with gastrointestinal cancer.

    PubMed

    Gomes de Lima, K V; Maio, R

    2012-01-01

    Systemic inflammatory response in individuals with cancer is related to a progressive reduction in total body mass, especially lean mass. The aim of the present study was to determine the association between nutritional status and systemic inflammatory response in patients with gastrointestinal cancer. A case series study was carried out involving 30 male and female adults and elderly patients with no prior treatment sent consecutively for surgery. Nutritional status was assessed using subjective and objective methods. Inflammatory response and prognosis were assessed through the determination of C-reactive protein (CRP), the Glasgow Prognostic Score and CRP/albumin ratio. High prevalence values were found for systemic inflammation (73%), a greater risk of infectious and/or inflammatory complication (43%) and worse prognosis (50%). The percentage of weight loss was correlated with serum CRP (r = 0.38; p < 0.05) and the CRP/albumin ratio (r = 0.44; p < 0.05). Inflammation markers and prognosis were negatively correlated with serum albumin (r = -0.50; p < 0.05), body mass index (r = -0.39; p < 0.05) and total lymphocyte count (r = -0.37; p < 0.05). Patients with weight loss and malnourishment had significantly higher serum CRP and CRP/albumin ratio values as well as lower serum albumin levels in comparison to those without weight loss and in well-nourished. Nutritional status is related to inflammation markers and prognosis in patients with gastrointestinal cancer. The diagnosis and attenuation of systemic inflammation should be part of the nutritional care of these patients.

  2. Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer.

    PubMed

    Qu, Ning; Zhang, Ling; Wu, Wei-Li; Ji, Qing-Hai; Lu, Zhong-Wu; Zhu, Yong-Xue; Lin, Dao-Zhe

    2016-07-01

    Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070-7.933), distant metastasis (HR = 3.860, 95 % CI 1.507-9.884), and cancer death (HR = 7.252, 95 % 2.189-24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185-4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300-19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

  3. Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy.

    PubMed

    Fagerholm, Rainer; Faltinova, Maria; Aaltonen, Kirsi; Aittomäki, Kristiina; Heikkilä, Päivi; Halttunen-Nieminen, Mervi; Nevanlinna, Heli; Blomqvist, Carl

    2017-10-10

    Long term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast cancer (BCS), distant disease free survival (DDFS), and local recurrence free survival (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95% CI 0.41-0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40-0.85; p = 0.005), with a consistent but not statistically significant effect in LRFS. This effect was not seen in familial cases (HR > 1.0), and family history was found to interact with HT in BCS (p(interaction) = 0.0067) (BC-death) and DDFS (p(interaction) = 0.0070). There was phenotypic heterogeneity between HT-associated tumors in familial and non-familial cases, particularly on estrogen receptor (ER) status, although the interaction between HT and family history appears to be at least partially independent of these markers (p = 0.0370 after adjustment for standard prognostic factors). If confirmed by further studies, our results suggest that family history should be taken into consideration in clinical counseling before beginning a HT regimen.

  4. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients.

    PubMed

    Henrique, Rui; Ribeiro, Franclim R; Fonseca, Daniel; Hoque, Mohammad O; Carvalho, André L; Costa, Vera L; Pinto, Mafalda; Oliveira, Jorge; Teixeira, Manuel R; Sidransky, David; Jerónimo, Carmen

    2007-10-15

    Prostate cancer is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. Owing to the limitations of current clinical, serologic, and pathologic parameters in predicting disease progression, we sought to investigate the prognostic value of promoter methylation of a small panel of genes by quantitative methylation-specific PCR (QMSP) in prostate biopsies. Promoter methylation levels of APC, CCND2, GSTP1, RARB2, and RASSF1A were determined by QMSP in a prospective series of 83 prostate cancer patients submitted to sextant biopsy. Clinicopathologic data [age, serum prostate-specific antigen (PSA), stage, and Gleason score] and time to progression and/or death from prostate cancer were correlated with methylation findings. Log-rank test and Cox regression model were used to identify which epigenetic markers were independent predictors of prognosis. At a median follow-up time of 45 months, 15 (18%) patients died from prostate cancer, and 37 (45%) patients had recurrent disease. In univariate analysis, stage and hypermethylation of APC were significantly associated with worse disease-specific survival, whereas stage, Gleason score, high diagnostic serum PSA levels, and hypermethylation of APC, GSTP1, and RASSF1A were significantly associated with poor disease-free survival. However, in the final multivariate analysis, only clinical stage and high methylation of APC were significantly and independently associated with unfavorable prognosis, i.e., decreased disease-free and disease-specific survival. High-level APC promoter methylation is an independent predictor of poor prognosis in prostate biopsy samples and might provide relevant prognostic information for patient management.

  5. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  6. The Associations between Immunity-Related Genes and Breast Cancer Prognosis in Korean Women

    PubMed Central

    Choi, Jaesung; Song, Nan; Han, Sohee; Chung, Seokang; Sung, Hyuna; Lee, Ji-young; Jung, Sunjae; Park, Sue K.; Yoo, Keun-Young; Han, Wonshik; Lee, Jong Won; Noh, Dong-Young; Kang, Daehee; Choi, Ji-Yeob

    2014-01-01

    We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell’s C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR) = 11.99, 95% CI = 3.62–39.72, P = 4.84E-05), rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10–8.62, P = 5.99E-05) and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18–9.87, P = 7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI = 1.48–31.06) compared to patients in the 1st tertile of polygenic risk score. Harrell’s C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women. PMID:25075970

  7. A coupling approach of a predictor and a descriptor for breast cancer prognosis

    PubMed Central

    2014-01-01

    Background In cancer prognosis research, diverse machine learning models have applied to the problems of cancer susceptibility (risk assessment), cancer recurrence (redevelopment of cancer after resolution), and cancer survivability, regarding an accuracy (or an AUC--the area under the ROC curve) as a primary measurement for the performance evaluation of the models. However, in order to help medical specialists to establish a treatment plan by using the predicted output of a model, it is more pragmatic to elucidate which variables (markers) have most significantly influenced to the resulting outcome of cancer or which patients show similar patterns. Methods In this study, a coupling approach of two sub-modules--a predictor and a descriptor--is proposed. The predictor module generates the predicted output for the cancer outcome. Semi-supervised learning co-training algorithm is employed as a predictor. On the other hand, the descriptor module post-processes the results of the predictor module, mainly focusing on which variables are more highly or less significantly ranked when describing the results of the prediction, and how patients are segmented into several groups according to the trait of common patterns among them. Decision trees are used as a descriptor. Results The proposed approach, 'predictor-descriptor,' was tested on the breast cancer survivability problem based on the surveillance, epidemiology, and end results database for breast cancer (SEER). The results present the performance comparison among the established machine leaning algorithms, the ranks of the prognosis elements for breast cancer, and patient segmentation. In the performance comparison among the predictor candidates, Semi-supervised learning co-training algorithm showed best performance, producing an average AUC of 0.81. Later, the descriptor module found the top-tier prognosis markers which significantly affect to the classification results on survived/dead patients: 'lymph node

  8. A coupling approach of a predictor and a descriptor for breast cancer prognosis.

    PubMed

    Shin, Hyunjung; Nam, Yonghyun

    2014-01-01

    In cancer prognosis research, diverse machine learning models have applied to the problems of cancer susceptibility (risk assessment), cancer recurrence (redevelopment of cancer after resolution), and cancer survivability, regarding an accuracy (or an AUC--the area under the ROC curve) as a primary measurement for the performance evaluation of the models. However, in order to help medical specialists to establish a treatment plan by using the predicted output of a model, it is more pragmatic to elucidate which variables (markers) have most significantly influenced to the resulting outcome of cancer or which patients show similar patterns. In this study, a coupling approach of two sub-modules--a predictor and a descriptor--is proposed. The predictor module generates the predicted output for the cancer outcome. Semi-supervised learning co-training algorithm is employed as a predictor. On the other hand, the descriptor module post-processes the results of the predictor module, mainly focusing on which variables are more highly or less significantly ranked when describing the results of the prediction, and how patients are segmented into several groups according to the trait of common patterns among them. Decision trees are used as a descriptor. The proposed approach, 'predictor-descriptor,' was tested on the breast cancer survivability problem based on the surveillance, epidemiology, and end results database for breast cancer (SEER). The results present the performance comparison among the established machine leaning algorithms, the ranks of the prognosis elements for breast cancer, and patient segmentation. In the performance comparison among the predictor candidates, Semi-supervised learning co-training algorithm showed best performance, producing an average AUC of 0.81. Later, the descriptor module found the top-tier prognosis markers which significantly affect to the classification results on survived/dead patients: 'lymph node involvement', 'stage', 'site

  9. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    PubMed

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  10. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer

    PubMed Central

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-01-01

    Abstract The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer. From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed. Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474). The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer. PMID:27828865

  11. JAM-A expression positively correlates with poor prognosis in breast cancer patients.

    PubMed

    McSherry, Elaine A; McGee, Sharon F; Jirstrom, Karin; Doyle, Emma M; Brennan, Donal J; Landberg, Goran; Dervan, Peter A; Hopkins, Ann M; Gallagher, William M

    2009-09-15

    The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target.

  12. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer.

    PubMed

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-11-01

    The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer.From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed.Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474).The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer.

  13. STMN1 in colon cancer: expression and prognosis in Chinese patients.

    PubMed

    Zhang, H-Q; Guo, X; Guo, S-Q; Wang, Q; Chen, X-Q; Li, X-N; Guo, L-S

    2016-05-01

    To study the stathmin (STMN1) expression in colorectal cancer and tumor-adjacent normal tissue and discuss its prognostic significance in colon cancer. STMN1 was tested with qRT-PCR in 30 samples of fresh colon cancer tissue and tumor-adjacent issue, and with immunohistochemical SP method in 105 samples of fresh colon cancer tissue and tumor-adjacent issue to analyze the association between its expression and clinical pathological parameters. Clinical data was combined to study the relationship between STMN1 expression and 5-year survival rate. Univariate analysis and Cox multivariate regression were performed to study the correlation between STMN1 expression and prognosis. The mRNA and protein level of STMN1 were significantly higher in colon cancer samples than tumor-adjacent normal tissues (p<0.05). STMN1 expression was independent of patient age, gender or location, but significantly related to lymph node metastasis and TNM staging (p<0.05). Survival analysis by Kaplan-Meier method showed that STMN1 expression was significantly related with the survival of colon cancer patients. The median survival time of STMN1-positive patients (37.5 months) was significantly shorter than STMN1-negative patients (57.1 months, p<0.05). Cox multivariate regression indicated that STMN1 is independent prognostic factors predicting the development, invasion and metastasis of colon cancer (p<0.05). STMN1 overexpression in colon cancer is independently associated with improved survival and significantly related to the development of the disease. Our findings suggest that presence of a STMN1-prognosis interaction that potentially determines clinical outcome.

  14. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen.

    PubMed

    Bergman, L; Beelen, M L; Gallee, M P; Hollema, H; Benraadt, J; van Leeuwen, F E

    2000-09-09

    Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. We did a nationwide case-control study on the risk and prognosis of endometrial cancer after tamoxifen use for breast cancer. Information on tamoxifen use and other risk factors for endometrial cancer was obtained from 309 women with endometrial cancer after breast cancer (cases), and 860 matched controls with breast cancer but without endometrial cancer. For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53. Tamoxifen had been used by 108 (36.1%) of 299 cases and 245 (28.5%) controls (relative risk 1.5 [95% CI 1.1-2.0]). Risk of endometrial cancer increased with longer duration of tamoxifen use (p < 0.001), with relative risks of 2.0 (1.2-3.2) for 2-5 years and 6.9 (2.4-19.4) for at least 5 years compared with non-users. Endometrial cancers of stage III and IV occurred more frequently in long-term tamoxifen users (> or = 2 years) than in non-users (17.4% vs 5.4%, p=0.006). Long-term users were more likely than non-users to have had malignant mixed mesodermal tumours or sarcomas of the endometrium (15.4% vs 2.9%, p < or = 0.02), p53-positive tumours (31.4% vs 18.2%, p=0.05), and negative oestrogen-receptor concentrations (60.8% vs 26.2%, p < or = 0.001). 3-year endometrial-cancer-specific survival was significantly worse for long-term tamoxifen users than for non-users (76% for > or = 5 years, 85% for 2-5 years vs 94% for non-users, p=0.02). Long-term tamoxifen users have a worse prognosis of endometrial cancers, which seems to be due to less favourable histology and higher stage. However, the benefit of tamoxifen on breast-cancer survival far outweighs the increased mortality from endometrial cancer. Nevertheless, we

  15. Incidence of prostate cancer in Lithuania after introduction of the Early Prostate Cancer Detection Programme.

    PubMed

    Smailyte, G; Aleknaviciene, B

    2012-12-01

    In Lithuania, prostate-specific antigen (PSA) testing is offered to healthy asymptomatic men as a screening test in the population-based Early Prostate Cancer Detection Programme (EPCDP). The aim of this study was to analyse the incidence of prostate cancer before and after introduction of the EPCDP in Lithuania. Prostate cancer incidence and mortality data from the Lithuanian Cancer Registry were analysed for the period 1990-2008. Age-specific incidence and mortality data were adjusted to the European Standard Population. There have been extraordinary changes in the incidence of prostate cancer in Lithuania following introduction of the EPCDP, and there is strong evidence that these changes are the result of increased detection rates, especially in men of screening age. Further observation of changes in prostate cancer incidence and mortality in Lithuania may help to determine the extent to which PSA testing at the population level influences incidence and mortality in the general population.

  16. Identification of novel long non-coding RNA biomarkers for prognosis prediction of papillary thyroid cancer

    PubMed Central

    Li, Qiuying; Li, Haihong; Zhang, Lu; Zhang, Chunming; Yan, Wentao; Wang, Chao

    2017-01-01

    Papillary thyroid carcinoma (PTC) is the most frequent type of malignant thyroid tumor. Several lncRNA signatures have been established for prognosis prediction in some cancers. However, the prognostic value of lncRNAs has not been investigated in PTC yet. In this study, we performed genome-wide analysis of lncRNA expression profiles in a large cohort of PTC patients from The Cancer Genome Atlas and identified 111 differentially expressed lncRNAs between tumor and non-tumor samples and between recurrent and recurrence-free samples. From the 111 differentially expressed lncRNAs, four independent lncRNA biomarkers associated with prognosis were identified and were integrated into a four-lncRNA signature which classified the patients of training dataset into the high-risk group and low-risk group with significantly different overall survival (p=0.016, log-rank test). The prognostic value of the four-lncRNA signature was validated in the independent testing dataset. Multivariate analysis indicated that the four-lncRNA signature was an independent prognostic predictor. Moreover, identified four lncRNA biomarkers demonstrates good performance in predicting disease recurrence with AUC of 0.833 using leave one out cross-validation. Our study not only highlighted the potential role for lncRNAs to improve clinical prognosis prediction in patients with PTC and but also provided alternative biomarkers and therapeutic targets for PTC patients. PMID:28545026

  17. Value of audits in breast cancer screening quality assurance programmes.

    PubMed

    Geertse, Tanya D; Holland, Roland; Timmers, Janine M H; Paap, Ellen; Pijnappel, Ruud M; Broeders, Mireille J M; den Heeten, Gerard J

    2015-11-01

    Our aim was to retrospectively evaluate the results of all audits performed in the past and to assess their value in the quality assurance of the Dutch breast cancer screening programme. The audit team of the Dutch Reference Centre for Screening (LRCB) conducts triennial audits of all 17 reading units. During audits, screening outcomes like recall rates and detection rates are assessed and a radiological review is performed. This study investigates and compares the results of four audit series: 1996-2000, 2001-2005, 2003-2007 and 2010-2013. The analysis shows increased recall rates (from 0.66%, 1.07%, 1.22% to 1.58%), increased detection rates (from 3.3, 4.5, 4.8 to 5.4 per 1000) and increased sensitivity (from 64.5%, 68.7%, 70.5% to 71.6%), over the four audit series. The percentage of 'missed cancers' among interval cancers and advanced screen-detected cancers did not change (p = 0.4). Our audits not only provide an opportunity for assessing screening outcomes, but also provide moments of self-reflection with peers. For radiologists, an accurate understanding of their performance is essential to identify points of improvement. We therefore recommend a radiological review of screening examinations and immediate feedback as part of an audit. • Radiological review and immediate feedback are recommended as part of an audit. • For breast screening radiologists, audits provide moments of self-reflection with peers. • Radiological review of screening examinations provides insights in recall behaviour. • Accurate understanding of radiologists' performance is essential to identify points of improvement.

  18. [Relationship between PUMA and BIM expression in colorectal cancer and tumor invasion, metastasis and prognosis].

    PubMed

    Yuan, Hang; Tu, Shi-Liang; He, Xu-Jun

    2013-06-01

    To study p53 up-regulated modulator of apoptosis (PUMA) and bcl-2 interacting mediator of cell death (BIM) of the BH3-only protein family expression in colorectal cancer tissues and its relationship with colorectal cancer invasion, metastasis and prognosis. Immunohistochemical staining (EnVision) was used to detect PUMA/BIM expression in 30 cases of normal mucosa, 30 cases of colorectal adenoma and 142 cases of colorectal cancer tissues. PUMA in colorectal cancer tissues was positive expressed (82.4%), which was significantly lower than in the normal mucosa colorectal adenomas (96.7%) and normal mucosa tissues (96.7%) (both χ(2) = 3.93, P < 0.05). Positive expression rate of BIM in colorectal cancer tissues (62.7%) was significantly lower than that in colorectal adenomas and normal mucosa (96.7% and 90.0%) (χ(2) = 8.42 and 13.29, P < 0.01). PUMA and BIM in colorectal cancer tissues were positively correlated (r = 0.747, P = 0.000). PUMA expression was related to tumor differentiation (χ(2) = 11.87), invasion depth (χ(2) = 11.59), lymph node metastasis (χ(2) = 12.82), TNM stage (χ(2) = 33.47) and P-gp expression (χ(2) = 18.30), all P < 0.05, but not related to the patients' age, gender, tumor size, tumor histological type and GST-π expression (P > 0.05). BIM expression was related to tumor differentiation (χ(2) = 16.19), lymph node metastasis (χ(2) = 14.95), TNM stage (χ(2) = 52.66) and P-gp expression (χ(2) = 10.60) (P < 0.05), but not related to patients' age, sex, tumor size, tumor histological type, invasion depth and GST-π expression (P > 0.05). 1-, 3-, 5-year survival rates of the positive expression of PUMA/BIM in patients with colorectal cancer were significantly higher than that of PUMA/BIM in patients with negative expression (χ(2) = 6.10 and 27.6, P < 0.05). Cox multivariate analysis showed that lymph node metastasis (RR = 0.238), TNM stage (RR = 7.895), PUMA (RR = 1.691) and BIM (RR = 0.440) could be used as independent prognostic

  19. Diagnosis delay and follow-up strategies in colorectal cancer. Prognosis implications: a study protocol

    PubMed Central

    2010-01-01

    Background Controversy exists with regard to the impact that the different components of diagnosis delay may have on the degree of invasion and prognosis in patients with colorectal cancer. The follow-up strategies after treatment also vary considerably. The aims of this study are: a) to determine if the symptoms-to-diagnosis interval and the treatment delay modify the survival of patients with colorectal cancer, and b) to determine if different follow-up strategies are associated with a higher survival rate. Methods/Design Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragón and Valencia) during the period 2010-2012. Incident cases are included with anatomopathological confirmation of colorectal cancer (International Classification of Diseases 9th revision codes 153-154) that formed a part of a previous study (n = 953). At the time of diagnosis, each patient was given a structured interview. Their clinical records will be reviewed during the follow-up period in order to obtain information on the explorations and tests carried out after treatment, and the progress of these patients. Symptoms-to-diagnosis interval is defined as the time calculated from the diagnosis of cancer and the first symptoms attributed to cancer. Treatment delay is defined as the time elapsed between diagnosis and treatment. In non-metastatic patients treated with curative intention, information will be obtained during the follow-up period on consultations performed in the digestive, surgery and oncology departments, as well as the endoscopies, tumour markers and imaging procedures carried out. Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables. Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed. Discussion This study will make it possible to verify if the different

  20. Dub3 expression correlates with tumor progression and poor prognosis in human epithelial ovarian cancer.

    PubMed

    Zhou, Bo; Shu, Bin; Xi, Tao; Su, Ning; Liu, Jing

    2015-03-01

    Dub3 is a deubiquitinating enzyme. It is highly expressed in tumor-derived cell lines and has an established role in tumor proliferation. However, the role of Dub3 in human ovarian cancer remains unclear. Expression of Dub3 was evaluated in ovarian cancer tissues and cell lines by immunohistochemistry and Western blot analysis. The relationship between Dub3 expression and clinicopathological characteristics was analyzed. Using RNA interference, the effects of Dub3 on cell proliferation and apoptosis were investigated in ovarian cancer cell line. All normal ovary tissues exhibited very little or no Dub3 immunoreactivity. High levels of Dub3 expression were examined by immunohistochemical analysis in 13.3% of cystadenomas, in 30.0% of borderline tumors, and in 58.9% of ovarian carcinomas, respectively. Dub3 expression was significantly associated with lymph node metastasis and clinical staging (P<0.05). Multivariate survival analysis indicated that Dub3 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, the expression of Cdc25A was closely correlated with that of Dub3 in cancer cells and tissues. Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis. These data indicate that the Dub3 might be a valuable biomarker for the prediction of ovarian cancer prognosis and Dub3 inhibition might be a potential strategy for ovarian cancer treatment.

  1. Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis.

    PubMed

    Somnay, Yash R; Yu, Xiao-Min; Lloyd, Ricardo V; Leverson, Glen; Aburjania, Zviadi; Jang, Samuel; Jaskula-Sztul, Renata; Chen, Herbert

    2017-03-01

    Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact. Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients. The functional role of Notch3 was then investigated by upregulating its expression in a follicular thyroid cancer (FTC) cell line. Notch3 expression regressed across decreasingly differentiated, increasingly malignant thyroid specimens, correlated with clinicopathological attributes reflecting poor prognosis, and independently predicted survival following univariate and multivariate analyses. Overexpression of the active Notch3 intracellular domain (NICD3) in a gain-of-function FTC line led to functional activation of centromere-binding protein 1, while increasing thyroid-specific gene transcription. NICD3 induction also reduced tumor burden in vivo and initiated the intrinsic apoptotic cascade, alongside suppressing cyclin and B-cell lymphoma 2 family expression. Loss of Notch3 expression may be fundamental to the process of dedifferentiation that accompanies thyroid oncogenesis. Conversely, activation of Notch3 in thyroid cancer exerts an antiproliferative effect and restores elements of a differentiated phenotype. These findings provide preclinical rationale for evaluating Notch3 as a disease prognosticator and therapeutic target in advanced thyroid cancer. Cancer 2017;123:769-82. © 2016 American Cancer Society. © 2016 American Cancer Society.

  2. Non-targeted and targeted metabolomics approaches to diagnosing lung cancer and predicting patient prognosis

    PubMed Central

    Zhang, Xiaoli; Zhu, Xinyue; Wang, Caihong; Zhang, Haixia; Cai, Zhiming

    2016-01-01

    Lung cancer is the most common cause of cancer death in China. We characterized metabolic alterations in lung cancer using two analytical platforms: a non-targeted metabolic profiling strategy based on proton nuclear magnetic resonance (1H-NMR) spectroscopy and a targeted metabolic profiling strategy based on rapid resolution liquid chromatography (RRLC). Changes in serum metabolite levels during oncogenesis were evaluated in 25 stage I lung cancer patients and matched healthy controls. We identified 25 metabolites that were differentially regulated between the lung cancer patients and matched controls. Of those, 16 were detected using the non-targeted approach and 9 were identified using the targeted approach. Both groups of metabolites could differentiate between lung cancer patients and healthy controls with 100% sensitivity and specificity. The principal metabolic alternations in lung cancer included changes in glycolysis, lipid metabolism, choline phospholipid metabolism, one-carbon metabolism, and amino acid metabolism. The targeted metabolomics approach was more sensitive, accurate, and specific than the non-targeted metabolomics approach. However, our data suggest that both metabolomics strategies could be used to detect early-stage lung cancer and predict patient prognosis. PMID:27566571

  3. Mean platelet volume predicts chemotherapy response and prognosis in patients with unresectable gastric cancer

    PubMed Central

    LIAN, LIAN; XIA, YOU-YOU; ZHOU, CHONG; SHEN, XIAO-MING; LI, XIANG-LI; HAN, SHU-GUANG; ZHENG, YAN; GONG, FEI-RAN; TAO, MIN; LI, WEI

    2015-01-01

    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 the prediction of chemotherapy response and prognosis in patients with unresectable gastric cancer. A total of 128 patients with unresectable gastric cancer were included and divided according to the median values of baseline MPV (low MPV: <11.65 or high MPV: ≥11.65). A low baseline MPV level was correlated with reduced metastasis. The results showed that patients with a low baseline level of MPV improved response to chemotherapy. Changes in MPV were associated with therapeutic efficacy. Patients who remained in or were transferred into the low MPV level subgroup following first-line chemotherapy had improved response, compared to those remaining in or being transferred into the high MPV level group. The patients with a higher baseline MPV had decreased progression-free and overall survival ratios. Univariate and multivariate analyses revealed that baseline MPV was a prognostic factor affecting progression-free survival. In conclusion, the results showed that MPV measurements can provide important prognostic information for gastric cancer patients. PMID:26788144

  4. Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer.

    PubMed

    Zampronha, Rossana de Araújo Catão; Freitas-Junior, Ruffo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Barbaresco, Aline Almeida; Adad, Sheila Jorge; Oliveira, Amaurillo Monteiro de; Rassi, Amanda B; Oton, Glória Jabur Bittar

    2013-06-01

    This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p=0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p=0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy.

  5. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer.

    PubMed

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-02-15

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors.

  6. The Generation and Validation of a 20-Genes Model Influencing the Prognosis of Colorectal Cancer.

    PubMed

    Xie, Xiao-Jun; Liu, Ping; Cai, Chu-Dong; Zhuang, Ying-Ru; Zhang, Li; Zhuang, Hai-Wen

    2017-11-01

    Colorectal cancer is a common malignant tumor with high incidence affecting the digestive system. This study aimed to identify the key genes relating to prognosis of colorectal cancer and to construct a prognostic model for its risk evaluation. Gene expression profiling of colorectal cancer patients, GSE17537, was downloaded from Gene Expression Omnibus database (GEO). A total of 55 samples from patients ranging from stages 1 to 4 were available. Differentially expressed genes were screened, with which single factor survival analysis was performed to identify the response genes. Interacting network and KEGG enrichment analysis of responsive genes were performed to identify key genes. In return, Fisher enrichment analysis, literature mining, and Kaplan-Meier analysis were used to verify the effectiveness of the prognostic model. The 20-gene model generated in this study posed significant influences on the prognoses (P = 9.691065e-09). Significance was verified via independent dataset GSE38832 (P = 9.86581e-07) and GSE17536 (P = 2.741e-08). The verified effective 20-gene model could be utilized to predict prognosis of patients with colorectal cancer and would contribute to post-operational treatment and follow-up strategies. J. Cell. Biochem. 118: 3675-3685, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Raman spectroscopy, a potential tool in diagnosis and prognosis of castration-resistant prostate cancer

    NASA Astrophysics Data System (ADS)

    Wang, Lei; He, Dalin; Zeng, Jin; Guan, Zhenfeng; Dang, Qiang; Wang, Xinyang; Wang, Jun; Huang, Liqing; Cao, Peilong; Zhang, Guanjun; Hsieh, JerTong; Fan, Jinhai

    2013-08-01

    Purpose: We evaluated the feasibility of Raman spectroscopy (RS) in diagnosis and prognosis of castration-resistant prostate cancer (CRPC) in patients with prostate cancer (PC). Materials and methods: Raman spectra are detected from PC cell lines (LNCaP and C4-2) and tissues using a Labram HR 800 RS. Then, principal component analysis (PCA) and support vector machine (SVM) are applied for prediction. A leave-one-out cross-validation is used to train and test the SVM. Results: There are 50 qualified patients, including 33 with androgen-dependent prostate cancer (ADPC) and 17 with CRPC. The spectral changes at 1126, 1170, 1315 to 1338, and 1447 cm-1 between CRPC and ADPC are detected in both cells and tissues models, which are assigned to specific amino acids and DNA. PCA/SVM algorithm provided a sensitivity of 88.2% and a specificity of 87.9% for diagnosing CRPC tissues. Furthermore, 14 patients with ADPC progressed to CRPC within 12 months. These patients are separated into two groups depending on whether their cancers progressed to CRPC within 12 months. PCA/SVM could differentiate these two groups with a sensitivity of 85.7% and a specificity of 88.9%. Conclusions: RS has the potential in diagnosis and prognosis of CRPC in clinical practice.

  8. The Prognosis of Breast Cancer Patients after Mastectomy and Immediate Breast Reconstruction: A Meta-Analysis

    PubMed Central

    Gu, Yan

    2015-01-01

    Background An increasing number of patients with breast cancer are being offered immediate breast reconstruction (IBR). The aim of this study was to analyze the impact of IBR on the prognosis of patients with breast cancer. Methods We searched the electronic databases of Medline (Pubmed), ISI Web of Knowledge, Embase, and Google Scholar databases for studies reporting the overall recurrence, disease-free survival (DFS), and overall survival (OS) of patients after mastectomy only and mastectomy with IBR. With these data, we conducted a meta-analysis of the clinical outcomes. Results Fourteen studies, including 3641 cases and 9462 controls, matched our criteria. Relevant information was extracted from these 14 studies. There was no significant heterogeneity (P for Q-statistic > 0.10 and I2 < 25%). Patients who underwent IBR showed no increased risk of overall recurrence of breast cancer (RR = 0.89; 95% confidence interval [CI]: 0.75, 1.04; P = 0.14). Furthermore, patients receiving IBR had similar DFS (RR = 1.04; 95%CI: 0.99, 1.08); P = 0.10) and OS (RR = 1.02; 95%CI: 0.99, 1.05; P = 0.24)) as those of control patients. Conclusion This meta-analysis provides evidence that IBR does not have an adverse effect on prognosis. These data suggest that IBR is an appropriate and safe choice for patients with breast cancer. PMID:26024490

  9. Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer.

    PubMed

    Yoshida, Naoya; Harada, Kazuto; Baba, Yoshifumi; Kosumi, Keisuke; Iwatsuki, Masaaki; Kinoshita, Koichi; Nakamura, Kenichi; Sakamoto, Yasuo; Miyamoto, Yuji; Karashima, Ryuichi; Mima, Kosuke; Sawayama, Hiroshi; Ohuchi, Mayuko; Chikamoto, Akira; Imamura, Yu; Watanabe, Masayuki; Baba, Hideo

    2017-03-01

    The aim of this study is to confirm the predictive value of controlling nutritional status (CONUT), as a postoperative prognostic marker for esophageal cancer patients undergoing esophagectomy. We retrospectively analyzed 373 patients who underwent three-incision esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and March 2016. The patients were divided into three groups based on the degree of preoperative malnutrition as assessed by CONUT: normal, light malnutrition, and moderate or severe malnutrition. The patients with moderate or severe malnutrition experienced a significantly higher frequency of reoperation (normal or light malnutrition, 6.3%; moderate or severe malnutrition, 18.2%; P = 0.033) and a higher tendency for respiratory morbidities (normal or light malnutrition, 14.0%; moderate or severe malnutrition, 27.3%; P = 0.088). Cox regression analysis identified a significantly poor prognosis, in both overall survival (hazard ratio (HR), 3.56; 95% confidence interval (CI), 1.714-7.390; P < 0.001) and cancer-specific survival (HR, 3.41; 95% CI, 1.790-6.516; P = 0.046). CONUT is convenient and useful for preoperatively assessing malnutrition and prognosis of esophageal cancer patients who underwent surgery.

  10. Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples

    PubMed Central

    Kazarian, Anna; Blyuss, Oleg; Metodieva, Gergana; Gentry-Maharaj, Aleksandra; Ryan, Andy; Kiseleva, Elena M; Prytomanova, Olga M; Jacobs, Ian J; Widschwendter, Martin; Menon, Usha; Timms, John F

    2017-01-01

    Background: Breast cancer is a leading cause of morbidity and mortality worldwide. Although mammography screening is available, there is an ongoing interest in improved early detection and prognosis. Herein, we have analysed a combination of serological biomarkers in a case–control cohort of sera taken before diagnosis. Methods: This nested case–control study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) used serum samples from 239 women who subsequently developed breast cancer and 239 matched cancer-free controls. Sera were screened by ELISA for 9 candidate markers. Univariate and multivariate analyses were performed to examine associations with clinico-pathological features and between case controls in different time groups before diagnosis. Results: Significant associations with clinico-pathological features related to prognosis were found for several candidates (CA15-3, HSP90A and PAI-1). However, there were no consistent differences between cases and controls for any candidate in the lead up to diagnosis. Whilst combination models outperformed single markers, there was no increase in performance towards diagnosis. Conclusions: This study using unique pre-diagnosis samples shows that CA15-3, HSP90A and PAI-1 have potential as early prognostic markers and warrant further investigation. However, none of the candidates or combinations would be useful for screening. PMID:28081538

  11. Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis?

    PubMed Central

    López-Basave, Horacio Noé; Morales-Vásquez, Flavia; Ruiz-Molina, Juan Manuel; Ñamendys-Silva, Silvio A; Vela-Sarmiento, Itzel; Ruan, Javier Melchor; Rosciano, Alejandro E Padilla; Calderillo-Ruiz, German; Díaz-Romero, Consuelo; Herrera-Gómez, Angel; Meneses-García, Abelardo A

    2013-01-01

    Background Gastric cancer is an aggressive disease with nonspecific early symptoms. Its incidence and prognosis in young patients has shown considerable variability. Purpose of the study Our objective was to retrospectively study patients from our institution aged <30 years with gastric carcinoma. The study was undertaken to describe the experience of gastric cancer in this population, and to demonstrate its specific clinical and pathological characteristics. Materials and methods We reviewed the cases of histologically confirmed gastric cancer between 1985 and 2006 at the Instituto Nacional de Cancerología of Mexico (INCan); emphasis in our review was placed on clinical presentation, diagnostic and therapeutic intervention, pathology, and the results. Results Thirty cases of gastric carcinoma were reviewed. The patients’ median age was 27 years (range, 18–30 years) and the male:female ratio was 1:1. Conclusion Gastric cancer exhibits different behavior in patients aged, 30 years, but delay in diagnosis and the tumor’s behavior appear to be the most important factors in prognosis of the disease. PMID:23580357

  12. Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer

    PubMed Central

    Tian, Yuan; Xu, Tangpeng; Huang, Jia; Zhang, Limin; Xu, Shan; Xiong, Bin; Wang, Yulan; Tang, Huiru

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors. PMID:26876567

  13. Pregnancy after treatment of breast cancer in young women does not adversely affect the prognosis.

    PubMed

    Córdoba, Octavi; Bellet, Meritxell; Vidal, Xavier; Cortés, Javier; Llurba, Elisa; Rubio, Isabel T; Xercavins, Jordi

    2012-06-01

    We assessed whether pregnancy after breast cancer in patients younger than 36 years of age affects the prognosis. Of 115 women with breast cancer followed for a mean of 6 years, 18 became pregnant (median time between diagnosis and the first pregnancy 44.5 months). Voluntary interruption of pregnancy was decided by 8 (44.4%) women. Significant differences in prognostic factors between pregnant and non-pregnant women were not observed. Pregnant women showed a lower frequency of positive estrogen receptors (41%) than non-pregnant (64%) (P=0.06). At 5 years of follow-up, 100% of women in the pregnant group and 80% in the non-pregnant group were alive. The percentages of disease-free women were 94% and 64%, respectively (P=0.009). Breast cancer patients presented a high number of unwanted pregnancies. Pregnancy after breast cancer not only did not adversely affect prognosis of the neoplasm but also may have a protective effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer

    PubMed Central

    de Araújo Catão Zampronha, Rossana; Freitas-Junior, Ruffo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Barbaresco, Aline Almeida; Adad, Sheila Jorge; de Oliveira, Amaurillo Monteiro; Rassi, Amanda B.; Oton, Glória Jabur Bittar

    2013-01-01

    OBJECTIVE: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. METHODS: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. RESULTS: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p = 0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p = 0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. CONCLUSION: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy. PMID:23778490

  15. Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer.

    PubMed

    Lee, Seungho; Choi, Seowon; Lee, Yookyung; Chung, Donghae; Hong, Suntaek; Park, Nohhyun

    2017-01-01

    Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study was designed to evaluate the role of HE4 in chemo-response against anti-cancer drugs and prognosis of epithelial ovarian cancer. HE4-depleted cells and HE4-overexpressing cells were generated. The effect of HE4 gene silencing and overexpression was examined using a cell viability assay after exposure to chemotherapeutic agents and the signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H-score. Knockdown of HE4 in OVCAR-3 cells resulted in reduction in cell growth and increased sensitivity to paclitaxel and cisplatin compared to control cells. This effect originated from the decreased activation of cell-growth-related signaling, such as AKT and Erk mediated by epidermal growth factor (EGF), while overexpression of HE4 resulted in enhanced cell growth and suppressed the anti-tumorigenic activity of paclitaxel. Activation of AKT and Erk pathways was enhanced in HE4-overexpressing cells compared to control cells. Based on the results of multivariate analysis, the risk of death was significantly higher in patients with an H-score > 4. HE4 induces chemoresistance against anti-cancer drugs and activates the AKT and Erk pathways to enhance tumor survival. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients. © 2016 Japan Society of Obstetrics and Gynecology.

  16. History of oral contraceptive use in breast cancer patients: impact on prognosis and endocrine treatment response.

    PubMed

    Huzell, Louise; Persson, Mia; Simonsson, Maria; Markkula, Andrea; Ingvar, Christian; Rose, Carsten; Jernström, Helena

    2015-01-01

    The purpose was to study oral contraceptive (OC) use in relation to breast cancer events and endocrine treatment response in a prospective population-based cohort, because it is unclear whether history of OC use impacts on prognosis in breast cancer patients. Between 2002 and 2011, 994 primary breast cancer patients without preoperative treatment were enrolled in Lund, Sweden and followed until December 2012. History of OC use was obtained from preoperative questionnaires. Tumor characteristics, clinical data, and date of death were obtained from pathology reports, patient charts, and population registries. Among the 948 patients with invasive cancer and no metastasis detected on the post-operative screen, 74 % had ever used OCs. Patients were followed for up to nine years (median follow-up 3 years), and 100 breast cancer events were recorded. Ever OC use was not associated with prognosis, irrespective of duration. However, any OC use before age 20 was associated with a threefold increased risk for breast cancer events in patients <50 years but not in patients ≥50 years (P interaction = 0.009). In patients ≥50 years with estrogen receptor positive tumors, previous OC use at any age was associated with a significantly decreased risk of breast cancer events among patients who received aromatase inhibitors compared to patients who never used OCs (adjusted HR 0.37: 95 % CI 0.15-0.87). OC use was not associated with tamoxifen-response. If confirmed, history of OC use may yield valuable prognostic and treatment predictive information in addition to currently used criteria.

  17. A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis.

    PubMed

    Ashour, Nadia; Angulo, Javier C; Andrés, Guillermo; Alelú, Raúl; González-Corpas, Ana; Toledo, María V; Rodríguez-Barbero, José M; López, Jose I; Sánchez-Chapado, Manuel; Ropero, Santiago

    2014-09-01

    DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors. Genome-wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered. We found 41 genes hypermethylated in more than 20% of the tumors analyzed (P < 0.01). Of these, we newly identified GSTM2 and PENK as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: a high Gleason score, elevated Ki-67, and advanced disease. Of these, we found simultaneous hypermethylation of CFTR and HTR1B to be common in patients with a high Gleason score and high Ki-67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer-specific mortality (log-rank test, P = 0.007) and biochemical recurrence-free survival (log-rank test, P = 0.0008). Our findings strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors. © 2014 Wiley Periodicals, Inc.

  18. Breastfeeding, PAM50 tumor subtype, and breast cancer prognosis and survival.

    PubMed

    Kwan, Marilyn L; Bernard, Philip S; Kroenke, Candyce H; Factor, Rachel E; Habel, Laurel A; Weltzien, Erin K; Castillo, Adrienne; Gunderson, Erica P; Maxfield, Kaylynn S; Stijleman, Inge J; Langholz, Bryan M; Quesenberry, Charles P; Kushi, Lawrence H; Sweeney, Carol; Caan, Bette J

    2015-07-01

    Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown. We conducted a cohort study of 1636 women from two prospective breast cancer cohorts. Intrinsic tumor subtype (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2]-enriched, basal-like) was determined by the PAM50 gene expression assay. Breastfeeding history was obtained from participant questionnaires. Questionnaires and medical record reviews documented 383 recurrences and 290 breast cancer deaths during a median follow-up of nine years. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between breastfeeding and tumor subtype. Cox regression was used to estimate hazard ratios (HRs) for breast cancer recurrence or death. Statistical significance tests were two-sided. Breast cancer patients with basal-like tumors were less likely to have previously breastfed than those with luminal A tumors (OR = 0.56, 95% CI = 0.39 to 0.80). Among all patients, ever breastfeeding was associated with decreased risk of recurrence (HR = 0.70, 95% CI = 0.53 to 0.93), especially breastfeeding for six months or more (HR = 0.63, 95% CI = 0.46 to 0.87, P trend = .01). Similar associations were observed for breast cancer death. Among women with luminal A subtype, ever breastfeeding was associated with decreased risks of recurrence (HR = 0.52, 95% CI = 0.31 to 0.89) and breast cancer death (HR = 0.52, 95% CI = 0.29 to 0.93), yet no statistically significant associations were observed among the other subtypes. Effects appeared to be limited to tumors with lower expression of proliferation genes. History of breastfeeding might affect prognosis and survival by establishing a luminal tumor environment with lower proliferative activity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Serum-based microRNA signatures in early diagnosis and prognosis prediction of colon cancer.

    PubMed

    Vychytilova-Faltejskova, Petra; Radova, Lenka; Sachlova, Milana; Kosarova, Zdenka; Slaba, Katerina; Fabian, Pavel; Grolich, Tomas; Prochazka, Vladimir; Kala, Zdenek; Svoboda, Marek; Kiss, Igor; Vyzula, Rostislav; Slaby, Ondrej

    2016-10-01

    Early detection of colorectal cancer is the main prerequisite for successful treatment and reduction of mortality. Circulating microRNAs were previously identified as promising diagnostic, prognostic and predictive biomarkers. The purpose of this study was to identify serum microRNAs enabling early diagnosis and prognosis prediction of colon cancer. In total, serum samples from 427 colon cancer patients and 276 healthy donors were included in three-phase biomarker study. Large-scale microRNA expression profiling was performed using Illumina small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs was validated on independent training and validation sets of samples using RT-qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four-microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c-3p was established (AUC = 0.917), distinguishing colon cancer patients from healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This panel of microRNAs exhibited high diagnostic performance also when analyzed separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC = 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66; P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs enabling non-invasive early detection and prognosis prediction of colon cancer were identified. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. High expression of REGγ is associated with metastasis and poor prognosis of patients with breast cancer.

    PubMed

    Chai, Fan; Liang, Yan; Bi, Jiong; Chen, Li; Zhang, Fan; Cui, Youhong; Bian, Xiuwu; Jiang, Jun

    2014-01-01

    REGgamma (REGγ) has been recently found in several types of human cancer, however, its clinical significance in metastasis and prognosis of breast cancer remains unknown. In this study, immunohistochemical staining and western blot analysis were performed to evaluate REGγ expression in both mouse and human breast cancer specimens. We found that in MMTV-PyMT mice, 14 out of 20 (70%) mouse mammary carcinomas were REGγ positive, which was significantly higher than control (0/20, 0%, P < 0.001) and lower than metastatic lung tumour (20/20, 100%, P = 0.027). Further investigation for REGγ expression in 136 human breast cancer tissues with the paired peritumoural normal breast tissues and 140 breast benign disease tissue samples showed that REGγ was undetectable in normal breast tissues and nonmetastatic axillary lymph nodes (ALNs), whereas 111 out of 136 (81.6%) breast cancer tissue samples were REGγ positive, which was significantly higher than breast benign disease tissues (9/140, 6.4%, P < 0.001) and lower than metastatic ALNs (116/116, 100%, P < 0.001). The 5-year disease-free and overall survivals of patients with negative/low level of REGγ were significantly higher than those of patients with high level of REGγ (P < 0.05). Cox regression analyses further indicated that REGγ could serve as a novel independent prognostic factor for breast cancer (OR = 4.369, P = 0.008). Our results suggest that the high expression of REGγ might predict metastasis and poor prognosis in breast cancer.

  1. Fucosylated Glycans in α1-Acid Glycoprotein for Monitoring Treatment Outcomes and Prognosis of Cancer Patients

    PubMed Central

    Yazawa, Shin; Takahashi, Ryo; Yokobori, Takehiko; Sano, Rie; Mogi, Akira; Saniabadi, Abby R.; Kuwano, Hiroyuki; Asao, Takayuki

    2016-01-01

    One standard treatment option for advanced-stage cancer is surgical resection of malignant tumors following by adjuvant chemotherapy and chemoradiotherapy. Additionally, neoadjuvant chemotherapy may be applied if required. During the time course of treatments, patients are generally followed by computed tomography (CT) surveillance, and by tumor marker diagnosis. However, currently, early evidence of recurrence and/or metastasis of tumors with a clinically relevant biomarker remains a major therapeutic challenge. In particular, there has been no validated biomarker for predicting treatment outcomes in therapeutic settings. Recently, we have looked at glycoforms of serum α1-acid glycoprotein (AGP) by using a crossed affinoimmunoelectrophoresis with two lectins and an anti-AGP antibody. The primary glycan structures of AGP were also analyzed by a mass spectrometer and a novel software in a large number of patients with various cancers. Accordingly, the relative abundance of α1,3fucosylated glycans in AGP (FUCAGP) was found to be significantly high in cancer patients as compared with the healthy controls. Further, strikingly elevated levels of FUCAGP were found in patients with poor prognosis but not in patients with good prognosis. In the current study, levels of FUCAGP in serum samples from various cancer patients were analyzed and 17 patients including 13 who had undergone chemotherapy were followed for several years post operation. FUCAGP level determined diligently by using a mass spectrometer was found to change along with disease prognosis as well as with responses to treatments, in particular, to various chemotherapies. Therefore, FUCAGP levels measured during following-up of the patients after operation appeared to be clinically relevant biomarker of treatment intervention. PMID:27295180

  2. Cystic brain metastasis is associated with poor prognosis in patients with advanced breast cancer

    PubMed Central

    Sun, Bing; Huang, Zhou; Wu, Shikai; Ding, Lijuan; Shen, Ge; Cha, Lei; Wang, Junliang; Song, Santai

    2016-01-01

    Purpose Brain metastasis (BM) with a cystic component from breast cancer is rare and largely uncharacterized. The purpose of this study was to identify the characteristics of cystic BM in a large cohort of breast cancer patients. Results A total of 35 eligible patients with cystic BM and 255 patients with solid BM were analyzed. Three factors were significantly associated with an increased probability of developing cystic lesions: age at diagnosis ≤ 40 years, age at BM ≤ 45 years, and poor histological grade (p < 0.05). Patients with cystic metastasis were also characterized by a larger metastasis volume, a shorter progression-free survival (PFS) following their first treatment for BM, and poor overall survival after BM (p < 0.05). Multivariate analysis further demonstrated that local control of cystic BM was only potentially achieved for HER2-negative primary tumors (p = 0.084). Methods Breast cancer patients with parenchymal BM were reviewed from consecutive cases treated at our institution. Cystic BM was defined when the volume of a cystic lesion was greater than 50% of the aggregated volume of all lesions present. Clinicopathologic and radiographic variables were correlated with development of cystic lesions and with prognosis of cystic BM. Conclusions This study shows that cystic BM from breast cancer, a special morphological type of BM, had worse prognosis than the more commonly observed solid BM. Younger age and low tumor grade were associated with the development of cystic lesions. Further comprehensive research and management of cystic BM are warranted to improve its poor prognosis. PMID:27659537

  3. Improved prognosis of breast cancer since 1970 in south-eastern Netherlands.

    PubMed Central

    Nab, H. W.; Hop, W. C.; Crommelin, M. A.; Kluck, H. M.; Coebergh, J. W.

    1994-01-01

    Despite many new advances in breast cancer therapy since the 1970s, there are only few reports on improved prognosis in a general population. A follow-up of more than 10 years is rarely reported, and a differentiation according to stage of the disease or between follow-up intervals is seldom made. Our purpose was to assess whether prognosis of primary breast cancer improved in patients diagnosed between 1970 and 1984 in south-eastern Netherlands, and to distinguish between different stages and follow-up intervals. Data from 4,467 breast cancer patients diagnosed between 1970 and 1984 were derived from the population-based Eindhoven Cancer Registry. Follow-up was attained up to 1 July 1991. Relative survival rates, as the ratio of the observed to the expected rates, were calculated. In a multivariate analysis a change in prognosis over time was computed with adjustment for age and stage; this was done separately for 5 year follow-up intervals. The relative survival rates were 69% after 5 years, 55% after 10 years and 50% after 20 years. Relative survival, after adjustment for age, was strongly related to the stage of the disease in the first 5 years of follow-up, less markedly between 5 and 10 years, and to a small, borderline significant, extent after 10 years of follow-up. Relative survival rates increased markedly over time, during the whole interval of follow-up. This increase was apparent in all age groups and in all stages, except for those with distant disease at diagnosis. The observed improvement in survival is unlikely to be explained by the increased use of adjuvant chemo- and hormonal therapy. Other factors, such as a change in the natural history of the disease in this period, cannot be ruled out. PMID:8054277

  4. Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers.

    PubMed

    Bing, Feng; Zhao, Yu

    2016-01-01

    To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan-Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20) and poor (such as ARID4A) prognoses following chemotherapy. Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A) in breast cancer patients.

  5. Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers

    PubMed Central

    Bing, Feng; Zhao, Yu

    2016-01-01

    Objective To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Methods Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan–Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. Results A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20) and poor (such as ARID4A) prognoses following chemotherapy. Conclusion Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A) in breast cancer patients. PMID:27217777

  6. Overexpression of Fli-1 is associated with adverse prognosis of endometrial cancer.

    PubMed

    Song, Wei; Zhang, Tianyang; Li, Wei; Mu, Rui; Zhang, Lingyi; Li, Yan; Jin, Baofeng; Wang, Na; Li, Ailing; Cui, Jiuwei

    2015-01-01

    This study aimed to investigate the expression of Friend leukemia virus integration 1 (Fli-1) and its correlation with the prognosis of endometrial cancer (EC). Thirty-two EC tissue samples were evaluated for Fli-1 expression using immunohistochemistry. Fli-1 showed significantly high expression in EC cells, followed by hyperplasia cells, and was negative in adjacent normal tissues. The high expression of Fli-1 was significantly associated with a high differentiation grade, mutated P53 expression, and histological subtype (p < .05). Downregulation of Fli-1 in AN3CN cells using RNA interference inhibited cell clone formation and proliferation but did not affect apoptosis and migration of the cells. This study provides the first evidence that Fli-1 expression gradually increases in parallel with disease progression, and its overexpression might predict poor prognosis in EC.

  7. Clinical Value of Prognosis Gene Expression Signatures in Colorectal Cancer: A Systematic Review

    PubMed Central

    Cordero, David; Riccadonna, Samantha; Solé, Xavier; Crous-Bou, Marta; Guinó, Elisabet; Sanjuan, Xavier; Biondo, Sebastiano; Soriano, Antonio; Jurman, Giuseppe; Capella, Gabriel; Furlanello, Cesare; Moreno, Victor

    2012-01-01

    Introduction The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. Methods A literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. Results Five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. Conclusions The published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic. PMID:23145004

  8. Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?

    PubMed

    Bigley, Austin B; Spielmann, Guillaume; LaVoy, Emily C P; Simpson, Richard J

    2013-09-01

    Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients.

  9. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Luo, Yi-Pey; Chen, Yi-Ling

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin‑embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer.

  10. NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer.

    PubMed

    Shi, Ce; Qin, Ling; Gao, Hongyu; Gu, Lina; Yang, Chang; Liu, Hebing; Liu, Tianbo

    2017-09-01

    NUCKS (nuclear, casein kinase, and cyclin-dependent kinase substrate) is implicated in the tumorigenesis of several human malignancies, but its role in ovarian cancer remains unknown. We aim to investigate NUCKS expression and its clinical significance in ovarian cancer. The messenger RNA expression of NUCKS was determined in normal and malignant ovarian tissues using quantitative polymerase chain reaction assay. Immunohistochemistry was applied to detect the status of NUCKS protein expression in 121 ovarian cancer tissues. NUCKS protein high expression was detected in 52 (43.0%) of 121 patients. NUCKS messenger RNA expression was gradually upregulated in non-metastatic ovarian cancers ( n = 20), metastatic ovarian cancers ( n = 20), and its matched metastatic lesions ( n = 20) in comparison with that in normal ovarian tissues ( n = 10; p < 0.05). Elevated expression of NUCKS in ovarian cancer was associated significantly with the Federation of Gynecology and Obstetrics stage ( p = 0.037), histological grade ( p = 0.003), residual disease ( p = 0.013), lymph node metastasis ( p = 0.002), response to chemotherapy ( p < 0.001), and recurrence ( p = 0.013). In the multivariate Cox analysis, NUCKS expression was an independent prognostic marker for overall survival and disease-free survival in ovarian cancer with p values of <0.001 for both. Especially, NUCKS overexpression had prognostic potential for overall survival and disease-free survival ( p < 0.001 for both) in advanced ovarian cancers and only for disease-free survival in early ovarian cancers ( p = 0.017). Our data suggest that NUCKS overexpression may contribute to progression and poor prognosis in ovarian cancer especially in advanced ovarian cancer.

  11. Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer.

    PubMed

    Ghanipour, L; Jirström, K; Sundström, M; Glimelius, B; Birgisson, H

    2017-02-01

    Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Role of cytokines in genesis, progression and prognosis of cervical cancer.

    PubMed

    Paradkar, Prajakta Hemant; Joshi, Jayashree Vinay; Mertia, Priyanka Nirmalsingh; Agashe, Shubhada Vidyadhar; Vaidya, Rama Ashok

    2014-01-01

    Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

  13. CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

    PubMed

    Chu, Dake; Zhu, Shaojun; Li, Jipeng; Ji, Gang; Wang, Weizhong; Wu, Guosheng; Zheng, Jianyong

    2014-01-01

    CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

  14. [Body weight, nutritional factors and physical activity--their influence on prognosis after breast cancer diagnosis].

    PubMed

    Weitzen, Rony; Tichler, Thomas; Kaufman, Bella; Catane, Raphael; Shpatz, Yael

    2006-11-01

    Numerous studies have examined the association between body weight, nutritional factors, physical activity and the risk for primary breast cancer. Relatively few studies, however, have examined the associations between these issues and the recurrence of the disease and cure of the primary tumor. Today, three areas of focus are actively being researched for breast cancer survivors: body weight, diet composition and physical activity with specific emphasis on the risk for recurrence, survival and quality of life. Increased body weight or BMI (Body Mass Index) at diagnosis was found to be a significant risk factor for recurrent disease, decreased survival, or both. Overall obesity has been shown to adversely affect prognosis. Appropriate weight control may be particularly beneficial for breast cancer survivors. Breast cancer survivors should be encouraged to achieve and maintain a healthy weight. Limiting fat intake can reduce the risk of breast cancer recurrence. Increasing consumption of vegetables and fruits seems to have possible beneficial effects during and after treatments. To date physical activity after breast cancer diagnosis has been found to reduce the risk of death. The greatest benefit occurred in women who performed the equivalent of walking 3-5 hours per week at an average pace. Safe weight loss via increased physical activity and healthful food choices should be encouraged for normal, overweight or obese breast cancer survivors in order to improve survival and life quality.

  15. Impact of Body Weight and Body Composition on Ovarian Cancer Prognosis.

    PubMed

    Purcell, Sarah A; Elliott, Sarah A; Kroenke, Candyce H; Sawyer, Michael B; Prado, Carla M

    2016-02-01

    Measures of body weight and anthropometrics such as body mass index (BMI) are commonly used to assess nutritional status in clinical conditions including cancer. Extensive research has evaluated associations between body weight and prognosis in ovarian cancer patients, yet little is known about the potential impact of body composition (fat mass (FM) and fat-free mass (FFM)) in these patients. Thus, the purpose of this publication was to review the literature (using PubMed and EMBASE) evaluating the impact of body weight and particularly body composition on surgical complications, morbidity, chemotherapy dosing and toxicity (as predictors of prognosis), and survival in ovarian cancer patients. Body weight is rarely associated with intra-operative complications, but obesity predicts higher rates of venous thromboembolism and wound complications post-operatively in ovarian cancer patients. Low levels of FM and FFM are superior predictors of length of hospital stay compared to measures of body weight alone, but the role of body composition on other surgical morbidities is unknown. Obesity complicates chemotherapy dosing due to altered pharmacokinetics, imprecise dosing strategies, and wide variability in FM and FFM. Measurement of body composition has the potential to reduce toxicity if the results are incorporated into chemotherapy dosing calculations. Some findings suggest that excess body weight adversely affects survival, while others find no such association. Limited studies indicate that FM is a better predictor of survival than body weight in ovarian cancer patients, but the direction of this relationship has not been determined. In conclusion, body composition as an indicator of nutritional status is a better prognostic tool than body weight or BMI alone in ovarian cancer patients.

  16. Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis

    PubMed Central

    Lippitz, Bodo E.; Harris, Robert A.

    2016-01-01

    ABSTRACT Objective: In tumor patients, IL-6 appears to be one component of a consistent cancer-associated cytokine network resulting in both a systemic immune stimulation and a microenvironment of cancer-induced immune suppression that ultimately protects the cancer cells. IL-6 has been associated with prognosis in cancer patients, but so far a systemical analysis has not been carried out. Methods: The present meta-analysis studies the relation between IL-6 serum levels and the prognosis of cancer patients in the available clinical literature of 100 articles published between 1993 and 2013 comprising 11,583 patients. Results: The IL-6 serum level was described as significantly correlating with survival in 82/101 series comprising 85.6% of patients (9917/11,583) with 23 different cancer types. A total of 64 studies dichotomized patient cohorts according to various cut-off IL-6 serum levels: in 59/64 of these series corresponding to 94.5% of the reported patients (7694/8142) significant correlations between IL-6 serum level and survival were seen. The median survival of cancer patients had been determined above various cut-off levels of serum IL-6 in 24 dichotomized studies (26 cohorts). There was a highly significant inverse correlation between median survival of the cohorts with IL-6 serum level above cut-off (1272 patients) and their corresponding IL-6 cut-off values (Spearman R -0,48 p= < 0.001) following a linear regression when both parameters were log-transformed (p < 0.001). A significant correlation between increasing serum IL-6 and tumor stage or metastases was described in 39/44 studies and 91% of published patients (4221/4636) where clinical parameters had been specified. Conclusions: Closely associated with the patient's clinical condition and independent of the cancer histology, the increased IL-6 serum level uniformly appears to correlate with survival as paraneoplastic condition in later cancer stages independent of the cancer type. Modifications of

  17. Combination Twist1 and CA15-3 in axillary lymph nodes for breast cancer prognosis

    PubMed Central

    Jiang, Xiaowei; Guo, Dan; Li, Wenfang; Yu, Tianwu; Zhou, Jian; Gong, Jianping

    2017-01-01

    Twist1 overexpression is involved in epithelial-mesenchymal transition resulting in migration and metastasis of breast cancer. Carcinoma antigen 15–3 (CA15-3) is widely used to monitor the prognosis for patients after treatment. However, the significance of Twist1 in axillary lymph nodes (ALN) and CA15-3 for co-examination for survival rates remains to be elucidated. The present study aimed to explore the role of the combination of Twist1 expression in metastasized ALN and the serum level of CA15-3 in evaluating the prognosis of patients with breast cancer. cluster of differentiation (CD)44, CD24, aldehyde dehydrogenase (ALDH)1 and Twist1 expression in normal and metastasized ALN from 102 patients with breast cancer were detected using laser confocal microscopy and the expression of the genes evaluated by reverse transcription-quantitative polymerase chain reaction; E-cadherin, N-cadherin and vimentin expression was also tested by western blotting. The serum concentrations of CA15-3 prior to and following surgery were analyzed by chemiluminescence immunoassay. The expression of CD44, ALDH1 and Twist1 mRNA in the primary breast cancer tissues and involved ALN was upregulated compared with the normal ALN (P<0.05). The proteins N-cadherin and vimentin of the involved ALN were poorly expressed compared with breast cancer tissues, however E-cadherin protein expression was higher in metastasized and normal ALN compared with primary cancer tissues (P<0.05). Of the 102 patients, the serum CA15-3 levels of the patients in stages I and II were significantly lower compared with stages III and IV (P<0.05). Twist1+/CA15-3+, HER2-negative/Twist1+/CA15-3+ and Triple-receptor negative/Twist1+/CA15-3+ groups displayed a shorter progression-free survival compared with others. The results of the present study demonstrated that CD44, ALDH1 and Twist1 were significantly overexpressed in involved ALN. The serum levels of CA15-3 in those patients were clearly increased and the survival

  18. CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis

    PubMed Central

    Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K.; Pépin, David

    2016-01-01

    CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be

  19. CD44 Gene Polymorphisms in Breast Cancer Risk and Prognosis: A Study in North Indian Population

    PubMed Central

    Tulsyan, Sonam; Agarwal, Gaurav; Lal, Punita; Agrawal, Sushma; Mittal, Rama Devi; Mittal, Balraj

    2013-01-01

    Background Cell surface biomarker CD44 plays an important role in breast cancer cell growth, differentiation, invasion, angiogenesis and tumour metastasis. Therefore, we aimed to investigate the role of CD44 gene polymorphisms in breast cancer risk and prognosis in North Indian population. Materials & Methods A total of 258 breast cancer patients and 241 healthy controls were included in the case-control study for risk prediction. According to RECIST, 114 patients who received neo-adjuvant chemotherapy were recruited for the evaluation of breast cancer prognosis. We examined the association of tagging SNP (rs353639) of Hapmap Gujrati Indians in Houston (GIH population) in CD44 gene along with a significant reported SNP (rs13347) in Chinese population by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. In-silico analysis for prediction of functional effects was done using F-SNP and FAST-SNP. Results No significant association of both the genetic variants of the CD44 gene polymorphisms was found with breast cancer risk. On performing univariate analysis with clinicopathological characteristics and treatment response, we found significant association of genotype (CT+TT) of rs13347 polymorphism with earlier age of onset (P = 0.029, OR = 0.037). However, significance was lost in multivariate analysis. For rs353639 polymorphism, significant association was seen with clinical tumour size, both at the genotypic (AC+CC) (P = 0.039, OR = 3.02) as well as the allelic (C) (P = 0.042, OR = 2.87) levels. On performing multivariate analysis, increased significance of variant genotype (P = 0.017, OR = 4.29) and allele (P = 0.025, OR = 3.34) of rs353639 was found with clinical tumour size. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs353639 polymorphism. Conclusions These findings suggest that CD44 rs353639 genetic variants may have

  20. Serum 25-Hydroxyvitamin D Level Does Not Affect the Aggressiveness and Prognosis of Papillary Thyroid Cancer.

    PubMed

    Ahn, Hwa Young; Chung, Yun Jae; Park, Kwang-Yeol; Cho, Bo Youn

    2016-03-01

    Vitamin D deficiency has been known to be associated with the aggressiveness and prognosis of several cancers. This study evaluated the effect of preoperative serum vitamin D levels on the aggressiveness and prognosis of papillary thyroid cancer (PTC). In total, 820 patients with PTC were enrolled. 25-hydroxyvitamin D levels were measured in blood samples before surgery. Clinical, pathologic, and recurrence data were accessed to examine the prognostic effects of vitamin D. Patients were categorized into four quartiles by preoperative serum vitamin D levels. Of the enrolled patients, 795 (97%) had insufficient vitamin D levels (<30 ng/mL). Vitamin D levels showed positive correlations with age and body mass index (BMI), and negative correlations with serum thyrotropin levels and antithyroid peroxidase antibody titers. The association between vitamin D quartile and the risks of extrathyroidal invasion, lymph node metastasis, advanced cancer stages (III or IV), and risk of recurrence were not significant after adjusting for age, sex, BMI, preoperative ionized calcium, and parathyroid hormone. Additionally, serum vitamin D was not associated with recurrent or persistent PTC. Serum vitamin D levels are not associated with either disease aggressiveness or poor outcomes among patients with PTC and vitamin D insufficiency.

  1. Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer

    PubMed Central

    Einama, Takahiro; Abe, Hironori; Shichi, Shunsuke; Matsui, Hiroki; Kanazawa, Ryo; Shibuya, Kazuaki; Suzuki, Takashi; Matsuzawa, Fumihiko; Hashimoto, Taku; Kohei, Nakachi; Homma, Shigenori; Kawamura, Hideki; Taketomi, Akinobu

    2017-01-01

    In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.

  2. Patient–oncologist communication in advanced cancer: predictors of patient perception of prognosis

    PubMed Central

    Robinson, Tracy M.; Alexander, Stewart C.; Hays, Margie; Jeffreys, Amy S.; Olsen, Maren K.; Rodriguez, Keri L.; Pollak, Kathryn I.; Abernethy, Amy P.; Arnold, Robert; Tulsky, James A.

    2010-01-01

    Goals of work Advanced cancer patients’ perceptions of prognosis, which are often overly optimistic compared to oncologist estimates, influence treatment preferences. The predictors of patients’ perceptions and the effect of oncologist communication on patient understanding are unclear. This study was designed to identify the communication factors that influence patient–oncologist concordance about chance of cure. Materials and methods We analyzed audiorecorded encounters between 51 oncologists and 141 advanced cancer patients with good (n=69) or poor (n=72) concordance about chance of cure. Encounters were coded for communication factors that might influence oncologist–patient concordance, including oncologist statements of optimism and pessimism. Main results Oncologists made more statements of optimism (mean=3.3 per encounter) than statements of pessimism (mean=1.2 per encounter). When oncologists made at least one statement of pessimism, patients were more likely to agree with their oncologist's estimated chance of cure (OR=2.59, 95%CI=1.31–5.12). Statements of optimism and uncertainty were not associated with an increased likelihood that patients would agree or disagree with their oncologists about chance of cure. Conclusions Communication of pessimistic information to patients with advanced cancer increases the likelihood that patients will report concordant prognostic estimates. Communication of optimistic information does not have any direct effect. The best communication strategy to maximize patient knowledge for informed decision making while remaining sensitive to patients’ emotional needs may be to emphasize optimistic aspects of prognosis while also consciously and clearly communicating pessimistic aspects of prognosis. PMID:18196288

  3. Tumour-related factors and prognosis in breast cancer detected by screening.

    PubMed

    Olsson, A; Borgquist, S; Butt, S; Zackrisson, S; Landberg, G; Manjer, J

    2012-01-01

    Breast cancer detected by screening has an unexplained prognostic advantage beyond stage shift compared with cancers detected clinically. The aim was to investigate biological factors in invasive breast cancer, with reference to mode of detection and rate of death from breast cancer. Histology, oestrogen receptor α and β, progesterone receptor, human epidermal growth factor receptor (HER) 2, cyclin D1, p27, Ki-67 and perinodal growth were analysed in 466 tumours from a prospective cohort, the Malmö Diet and Cancer Study. Using logistic regression, odds ratios were calculated to investigate the relationship between tumour characteristics and mode of detection. The same tumour factors were analysed in relation to standard prognostic features. Death from breast cancer was analysed using Cox regression with adjustments for standard tumour factors; differences following adjustment were analysed by means of Freedman statistics. None of the biological tumour characteristics varied with mode of detection of breast cancer. After adjustment for age, tumour size, axillary lymph node involvement (ALNI) and grade, women with cancer detected clinically had an increased risk of death from breast cancer (hazard ratio 2·48, 95 per cent confidence interval 1·34 to 4·59), corresponding to a 37·2 per cent difference compared with the unadjusted model. Additional adjustment for biological tumour factors studied caused only minor changes. None of the biological tumour markers investigated explained the improved prognosis in breast cancer detected by screening. None of the factors was related to ALNI, suggesting that other mechanisms may be responsible for tumour spread. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  4. p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

    PubMed

    Iniesta, P; Vega, F J; Caldés, T; Massa, M; de Juan, C; Cerdán, F J; Sánchez, A; López, J A; Torres, A J; Balibrea, J L; Benito, M

    1998-08-14

    We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

  5. Musashi2 as a novel predictive biomarker for liver metastasis and poor prognosis in colorectal cancer.

    PubMed

    Zong, Zhen; Zhou, Taicheng; Rao, Liangjun; Jiang, Zhipeng; Li, Yingru; Hou, Zehui; Yang, Bin; Han, Fanghai; Chen, Shuang

    2016-04-01

    Aberrant expression of musashi2 (MSI-2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI-2 protein in patients with colorectal cancer. The expression of MSI-2 was detected in 164 patients' colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI-2 expression and clinicopathological variables including overall survival were analyzed. The prognostic value of liver metastasis is evaluated by logistic regression and receiver operating characteristic (ROC) analysis. MSI-2 was highly expressed in 32.9% (54/164) of the colorectal cancer. Overexpression of MSI-2 was associated with depth of invasion, lymph node metastasis, distant metastasis, liver metastasis, Tumor Node Metastasis (TNM) clinical stage, and Carcinoembryonicantigen (CEA) level (P = 0.040, 0.014, <0.001, <0.001, 0.003, and 0.002, respectively). In the Cox multivariate test, MSI-2 overexpression, lymph node metastasis, and distant metastasis were found to be the independent prognostic factors (P = 0.027, 0.010, and 0.001, respectively). Further logistic regression suggested that TNM stage and MSI-2 high expression were related to liver metastasis in colorectal cancer patients. Conclusively, our study indicates that MSI-2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients.

  6. Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

    PubMed

    Pang, Li; Wang, Da-Wei; Zhang, Nan; Xu, Da-Hai; Meng, Xiang-Wei

    2016-03-11

    Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

  7. Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer

    PubMed Central

    Qu, Yanchun; Zhang, Changwen; Du, E; Wang, Andi; Yang, Yuming; Guo, Jianing; Wang, Aixiang; Zhang, Zhihong; Xu, Yong

    2016-01-01

    Background Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. Material/Methods We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. Results We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. Conclusions Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese. PMID:27826135

  8. Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer prognosis and therapeutics.

    PubMed

    Yang, Meng; Liu, Yun-Duo; Wang, Yan-Ying; Liu, Tian-Bo; Ge, Ting-Ting; Lou, Ge

    2014-02-01

    Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor progression and oncogenesis. The aim of this study was to investigate the role of USP22 and the association with its potential targets in patients with cervical cancer. To our knowledge, this is the first study that determines the relationship between USP22 expression and clinicopathological significance in cervical cancer. The immunohistochemistry results showed that USP22 protein was overexpressed in cervical cancer samples compared with normal cervical tissues (P < 0.001). Moreover, clinicopathological analysis showed that USP22 expression was highly related to International Federation of Gynecology and Obstetrics stage, Ki67, lymph node metastasis, and histology grade. The results of Kaplan-Meier analysis indicated that patients with high USP22 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients with low expression of USP22 (P < 0.001). Multivariate Cox regression analysis revealed that USP22 expression status was an independent prognostic marker for both OS and DFS of patients with cervical cancer. It is suggested that USP22 overexpression may be associated with poor prognosis in cervical cancer. It may represent a novel prognostic biomarker or a target for improving the treatment efficiency of patients with cervical cancer.

  9. rs621554 single nucleotide polymorphism of DLC1 is associated with breast cancer susceptibility and prognosis.

    PubMed

    Ding, Xia; Gao, Sumei; Yang, Qifeng

    2016-05-01

    Deleted in liver cancer 1 (DLC1) on chromosome 8p22, is an important tumor suppressor gene originally identified to be deleted in hepatocellular carcinoma. It can regulate the structure of the actin cytoskeleton and inhibit cell proliferation, motility and angiogenesis, which predominantly depends on its homology to rat RhoGAP. There are many genetic variants in DLC1, which may influence its antitumor efficacy. The rs621554 (IVS19+108C>T) polymorphism is a synonymous single nucleotide polymorphism (SNP) previously found to be associated with hepatocellular carcinoma. In the present study, 453 patients with breast cancer and 330 healthy females were analyzed using a cycling probe method. It was determined that the rs621554 polymorphism of DLC1 was associated with breast cancer susceptibility, with the CC and CT genotypes resulting in a higher risk of developing breast cancer. In regard to clinicopathological variables, it was demonstrated that the CT and CC genotype were associated with tumor size, lymph node metastasis and progesterone receptor status. Patients with the CT and CC genotype had shorter disease-free survival and overall survival rates compared with those with the TT genotype. Additionally, it was demonstrated that the rs621554 polymorphism was correlated with DLC1 expression at the mRNA level. These results suggested that the rs621554 polymorphism is associated with breast cancer susceptibility and prognosis, and may serve as a biomarker for breast cancer development and progression.

  10. Low Stromal Area and High Stromal Microvessel Density Predict Poor Prognosis in Pancreatic Cancer.

    PubMed

    Nishida, Takahiro; Yoshitomi, Hideyuki; Takano, Shigetsugu; Kagawa, Shingo; Shimizu, Hiroaki; Ohtsuka, Masayuki; Kato, Atsushi; Furukawa, Katsunori; Miyazaki, Masaru

    2016-04-01

    Excessive stroma is a unique property of cancer tissue of the pancreas. The aim of this study was to analyze the relationship of cancer stromal area (SA) and tumor microvessel density (MVD) with prognostic and clinicopathological findings. Pancreatic adenocarcinoma tissues obtained from 104 patients were subjected to cytokeratin 19 and CD31 double immunostaining to identify cancer cells and endothelial cells simultaneously. Stromal area and MVD were assessed in the same sections. Patients were divided into 2 groups for each analysis by the median value of the respective measure. Stromal area negatively correlated with MVD. The low SA group harbored more poorly differentiated carcinoma than the high SA group. Patients of the low SA group showed a higher incidence of hematogenous recurrence. As a consequence, patients in the low SA and the high MVD groups had poorer prognosis in terms of both disease-free survival and overall survival than their respective groups. Multivariate analysis showed that a low SA was an independent prognostic factor for disease-free and overall survival. Our data indicate that the stroma of pancreatic cancer may play an auxiliary role as a barrier to cancer cell invasion. The depletion of tumor stroma alone does not suppress pancreatic cancer progression.

  11. Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

    PubMed

    Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

    2012-09-01

    Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

  12. Increased ZO-1 expression predicts valuable prognosis in non-small cell lung cancer

    PubMed Central

    Ni, Songshi; Xu, Liqin; Huang, Jianfei; Feng, Jian; Zhu, Huijun; Wang, Gui; Wang, Xudong

    2013-01-01

    Objective: The aim of this study was to investigate the expression of Zonula Occludens-1 (ZO-1) and its potential value as prognostic indicator of survival in patients with primary non-small cell lung cancer (NSCLC). Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry with tissue microarrays were used to characterize the expression of the ZO-1 mRNA and protein in NSCLC. The correlation of ZO-1 expression with clinical characteristics and prognosis was determined by statistical analysis. Results: The ZO-1 mRNA and protein levels were significantly lower in NSCLC tissue compared with corresponding peritumoral tissue (P<0.05). ZO-1 protein expression in NSCLC was related to age (P=0.042) and 5-year survival (P<0.001). Kaplan-Meier survival and Cox regression analyses revealed that low ZO-1 expression (P<0.001) and later stage grouping by TNM (P=0.031) were independent factors predicting poor prognosis for patients with NSCLC. Conclusions: Our findings provide the first evidence that high expression of ZO-1 is associated with good prognosis in NSCLC. PMID:24294375

  13. hTERT gene polymorphism correlates with the risk and the prognosis of thyroid cancer.

    PubMed

    Gong, Long; Xu, Ying; Hu, Ya-Qin; Ding, Qiu-Ju; Yi, Chun-Hua; Huang, Wei; Zhou, Ming

    2016-07-08

    The study explored the association between rs10069690C/T and rs2736100G/T of human telomerase reverse transcriptase (hTERT) gene, and the prognosis of thyroid cancer. The study had 452 thyroid cancer patients recruited as case group who hospitalized in Jingzhou Central Hospital from January 2001 to June 2004 and 452 healthy people recruited as control group at the same area. The hTERT gene polymorphisms at rs10069690 C/T and rs2736100 G/T were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between patients' life quality and hTERT gene polymorphisms six months after surgery was evaluated based on the Cancer patients' quality of life index rating scale. There were statistical differences in genotype and allele frequencies of rs10069690 C/T between the case group and control group (both P < 0.05). An association between rs10069690C/T polymorphism and an increased risk of thyroid cancer was shown by logistic regression analysis (CT vs. CC, OR = 1.333, 95%CI = 1.006-1.766, P = 0.045; TT vs. CC, OR = 1.910, 95%CI = 1.084-3.367, P = 0.023; CT + TT vs. CC, OR = 2.246, 95%CI = 1.078-1.840, P = 0.006; T vs. C, OR = 1.376, 95%CI = 1.104-1.715, P = 0.004). Genotype frequency of rs2736100G/T between the two groups had no statistical differences (P > 0.05). After stratification according to age, T stage, tumor size and tumor node metastasis (TNM) stage, the distribution frequencies of CC genotype and CT + TT genotype of rs10069690C/T showed significant difference (P < 0.05). The life quality of patients with CC genotype was better than that of patients with CT $+$ TT genotype. The results of Cox regression model multifactor analysis showed that age, T stage, tumor size and rs10069690C/T were independent risk factors of thyroid cancer prognosis. hTERT gene polymorphism at rs10069690C/T is associated with the risk and prognosis of thyroid cancer, but hTERT gene polymorphism at rs2736100G/T is not.

  14. Gene expression profile in the activation of subperitoneal fibroblasts reflects prognosis of patients with colon cancer.

    PubMed

    Yokota, Mitsuru; Kojima, Motohiro; Higuchi, Youichi; Nishizawa, Yuji; Kobayashi, Akihiro; Ito, Masaaki; Saito, Norio; Ochiai, Atsushi

    2016-03-15

    Tumors can create a heterogenetic tumor microenvironment. We recently identified the pathologically unique cancer microenvironment formed by peritoneal invasion (CMPI), and revealed that subperitoneal fibroblasts (SPFs) within peritoneal tissue play a crucial role in tumor progression through their interaction with cancer cells. Therefore, the genes in SPFs altered by cancer stimulation may include some biologically important factors associated with patient prognosis. In this study, we aimed to identify new biomarkers using genes specifically upregulated in SPFs by cancer-cell-conditioned medium (CCCM) stimulation (SPFs CCCM response genes; SCR genes) in colon cancer (CC). We constructed two frameworks using SCR gene data: a publicly released microarray dataset, and validation cases with freshly frozen CC samples to identify genes related to short recurrence-free survival (RFS). In the first framework, we selected differentially expressed genes between the high and low SCR gene expression groups. In the second framework, genes significantly related to short RFS were selected by univariate analysis using all SCR genes, and multivariate analysis was performed to select robust genes associated with short RFS. We identified CTGF, CALD1, INHBA and TAGLN in the first framework, and PDLIM5, MAGI1, SPTBN1 and TAGLN in the second framework. Among these seven genes, high expression of three genes (CALD1, TAGLN and SPTBN1) showed a poor prognosis in our validation cases. In a public microarray dataset, SCR gene expression was associated with the expression of ECM component, EMT, and M2-macrophage associated genes, which was concordant with the pathological features of CMPI. Thus, we successfully identified new prognostic factors.

  15. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers.

    PubMed

    Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Irahara, Natsumi; Chan, Andrew T; Meyerhardt, Jeffrey A; Chung, Daniel C; Giovannucci, Edward L; Fuchs, Charles S; Ogino, Shuji

    2010-05-01

    Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1alpha) and endothelial PAS domain protein 1 (EPAS1; HIF-2alpha), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index > or = 30 kg/m2) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications.

  16. The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis

    PubMed Central

    Li, Lu; Zhou, Ying; Wang, Chao; Hou, Shuxun

    2015-01-01

    Background Telomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting. Methods Prospective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals. Results Thirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06–1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10–1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios. Conclusion Short TL demonstrated a significant association with poor cancer survival, suggesting the

  17. Impact of Soy Foods on the Development of Breast Cancer and the Prognosis of Breast Cancer Patients.

    PubMed

    Messina, Mark

    2016-01-01

    The relationship between soy food intake and breast cancer has been rigorously investigated for more than 25 years. The identification of isoflavones as possible chemopreventive agents helped fuel this line of investigation. These diphenolic compounds, which are found in uniquely-rich amounts in soy beans, possess both estrogen-dependent and -independent properties that potentially inhibit the development of breast cancer. Observational studies show that among Asian women higher soy consumption is associated with an approximate 30% reduction in risk of developing breast cancer. However, evidence suggests that for soy to reduce breast cancer risk consumption must occur early in life, that is during childhood and/or adolescence. Despite the interest in the role of soy in reducing breast cancer risk concerns have arisen that soy foods, because they contain isoflavones, may increase the likelihood of high-risk women developing breast cancer and worsen the prognosis of breast cancer patients. However, extensive clinical and epidemiologic data show these concerns to be unfounded. Clinical trials consistently show that isoflavone intake does not adversely affect markers of breast cancer risk, including mammographic density and cell proliferation. Furthermore, prospective epidemiologic studies involving over 11,000 women from the USA and China show that postdiagnosis soy intake statistically significantly reduces recurrence and improves survival. © 2016 S. Karger GmbH, Freiburg.

  18. Nuclear overexpression of the overexpressed in lung cancer 1 predicts worse prognosis in gastric adenocarcinoma.

    PubMed

    Wang, Jue; Shen, Hongchang; Fu, Guobin; Zhao, Dandan; Wang, Weibo

    2017-02-07

    We have performed this retrospective study to elucidate whether elevated expression of the overexpressed in lung cancer 1 (OLC1) was related to the clinicopathological parameters and prognosis of patients with gastric adenocarcinoma. Additionally, different effects of various subcellular OLC1 expression on gastric adeno-carcinogenesis were focused on in our study. Both overall and subcellular expression of OLC1 was evaluated by immunohistochemistry(IHC) via tissue microarrays from total 393 samples. The Kaplan-Meier method and Cox's proportional hazard model were exerted to further explore the correlation between OLC1 and prognosis. Total overexpression of OLC1 was significantly associated with stage (P = 0.004) and differentiation (P = 0.009), and only the strong total expression could predict a poor prognosis (HR = 1.31, P = 0.04). There were significant associations found between nuclear overexpression and tumor invasion depth(P = 0.002), lymph node (P < 0.001), stage (P = 0.004), differentiation (P < 0.001) and smoking history (P = 0.045). Furthermore, over-expressed nuclear OLC1 protein could be an independent risk factor for gastric adenocarcinoma (univariate: HR = 1.43, P = 0.003; multivariate: HR = 1.39, P = 0.011). In general, both total and nuclear overexpression of OLC1 could be the signs of gastric adeno-carcinogenesis, which might be served as the biomarkers for diagnosis at an early stage, even at the onset of tumorigenesis. Rather than the total expression, nuclear overexpression of OLC1 was correlated with most clinicopathological parameters and could predict a poor overall survival as an independent factor for prognosis, which made it a more effective and sensitive biomarker for gastric adenocarcinoma.

  19. Aberrant DNA methylation impacts gene expression and prognosis in breast cancer subtypes.

    PubMed

    Győrffy, Balázs; Bottai, Giulia; Fleischer, Thomas; Munkácsy, Gyöngyi; Budczies, Jan; Paladini, Laura; Børresen-Dale, Anne-Lise; Kristensen, Vessela N; Santarpia, Libero

    2016-01-01

    DNA methylation has a substantial impact on gene expression, affecting the prognosis of breast cancer (BC) patients dependent on molecular subtypes. In this study, we investigated the prognostic relevance of the expression of genes reported as aberrantly methylated, and the link between gene expression and DNA methylation in BC subtypes. The prognostic value of the expression of 144 aberrantly methylated genes was evaluated in ER+/HER2-, HER2+, and ER-/HER2- molecular BC subtypes, in a meta-analysis of two large transcriptomic cohorts of BC patients (n = 1,938 and n = 1,640). The correlation between gene expression and DNA methylation in distinct gene regions was also investigated in an independent dataset of 104 BCs. Survival and Pearson correlation analyses were computed for each gene separately. The expression of 48 genes was significantly associated with BC prognosis (p < 0.05), and 32 of these prognostic genes exhibited a direct expression-methylation correlation. The expression of several immune-related genes, including CD3D and HLA-A, was associated with both relapse-free survival (HR = 0.42, p = 3.5E-06; HR = 0.35, p = 1.7E-08) and overall survival (HR = 0.50, p = 5.5E-04; HR = 0.68, p = 4.5E-02) in ER-/HER2- BCs. On the overall, the distribution of both positive and negative expression-methylation correlation in distinct gene regions have different effects on gene expression and prognosis in BC subtypes. This large-scale meta-analysis allowed the identification of several genes consistently associated with prognosis, whose DNA methylation could represent a promising biomarker for prognostication and clinical stratification of patients with distinct BC subtypes.

  20. [Methods to increase participation in cancer screening programmes].

    PubMed

    Giorgi Rossi, Paolo; Camilloni, Laura; Cogo, Carla; Federici, Antonio; Ferroni, Eliana; Furnari, Giacomo; Giordano, Livia; Grazzini, Grazia; Iossa, Anna; Jimenez, Beatriz; Palazzi, Mauro; Palazzo, Fabio; Spadea, Teresa; Senore, Carlo; Borgia, Piero; Guasticchi, Gabriella

    2012-01-01

    to synthesize scientific evidences about methods to increase cervical, breast and colorectal cancer screening participation. a multidisciplinary working group has been set up to define the scope of the report and to conduct the evaluation. The scope and the final evaluation have been submitted to a stakeholder committee, including the Ministry of Health, the National Screening Observatory, regional screening program coordinators, scientific societies, and Lega Italiana Lotta ai Tumori, for comments and integrations. A systematic review of the principal biomedical and social literature databases was conducted to identify experimental and observational studies, updating the existing review by Jepson and coll. (Health Technol Assess. 2000;4(14):i-vii, 1-133). 5900 have been identified, 900 relevant for the topic.Among those, 148 reported quantitative information on intervention efficacy, other 90 came from the previous review. Organised screening programmes, based on invitation letter or on GP involvement,were consistently effective in increasing participation compared to spontaneous screening. Interventions are classified according to their target: individual, community, test simplification, health operators, health service organization. The report presents meta-analyses on efficacy, analyses of cost-effectiveness, impact on organisation and social inequality, and ethical and legal issues, of all the intervention reported in the literature. there are several interventions consistently effective in any context, some of them have minimal impact on costs and health service resources.

  1. [Interval cancers and episode sensitivity in population-based screening programmes for colorectal cancer: a systematic review].

    PubMed

    Domènech, Xènia; Garcia, Montse; Benito, Llúcia; Binefa, Gemma; Vidal, Carmen; Milà, Núria; Moreno, Víctor

    2015-01-01

    To describe interval cancers (IC) and the sensitivity of colorectal cancer (CRC) screening programmes. A systematic review of the literature was conducted through a MEDLINE (PubMed) search. The search strategy combined the terms 'interval cancer', 'false negative', 'mass screening', 'screening' 'early detection of cancer', 'colorectal cancer' and 'bowel cancer'. Inclusion criteria consisted of population-based screening programmes, original articles written in English or Spanish and publication dates between 1999/01/01 and 2015/02/28. A narrative synthesis of the included articles was performed detailing the characteristics of the screening programmes, the IC rate, and the information sources used in each study. Thirteen articles were included. The episode sensitivity of CRC screening programmes ranged from 42.2% to 65.3% in programmes using the guaiac test and between 59.1% and 87.0% with the immunochemical test. We found a higher proportion of women who were diagnosed with IC and these lesions were mainly located in the proximal colon. There is wide variability in the IC rate in CRC programmes. To ensure comparability between programmes, there is a need for consensus on the working definition of IC and the methods used for their identification and quantification. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Breast cancer screening: characteristics and results of the Italian programmes in the Italian group for planning and evaluating breast cancer screening programmes (GISMa).

    PubMed

    Giordano, L; Giorgi, D; Fasolo, G; Segnan, N; Del Turco, M R

    1996-01-01

    In 1990, GISMa (Italian Group for planning and evaluating Mammographic Screening - Gruppo Italiano per la pianificazione e la valutazione dei programmi di Screening Mammografico), a working group of operators (radiographers, radiologists, epidemiologists, clinicians, surgeons) involved in screening programmes ongoing in Italy, was created within the Italian School of Senology. The aim of this study is to illustrate data, presented at the GISMa meeting held in April 1994, concerning the characteristics of each programme and some early indicators of effectiveness. To assess these parameters (concerning compliance level, recall rate, benign/malignant biopsy ratio, detection rate, stage distribution, nodal involvement and number of cancers with a diameter under 1 cm, rate of cancer, etc.), 'acceptable' and 'desirable' standards obtained from Italian and North-European cancer screening experiences have been adopted. Most programmes have shown an acceptable standard for most of the indicators, and many of them have attained desirable levels. In most screening programmes the occurrence of interval cancers has not yet been measured, but all centres have (or are working to set up) a systematic active procedure to collect the data. The results indicate that common guidelines can be adopted, even when working in very heterogeneous contexts, and that it is possible to achieve a very high effectiveness and efficacy level. As regards quality control and cost/benefit issues, the goal of extending centralised, population-based screening programmes to other Italian regions becomes a priority.

  3. Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer.

    PubMed

    Li, Xianxian; Xing, Hui; Li, Lin; Huang, Yanli; Zhou, Min; Liu, Qiong; Qin, Xiaomin; He, Min

    2014-03-01

    Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node (PAN) removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN + pelvic lymph node (PLN) dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B (P < 0.05). In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant (P > 0.05). The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate (P = 0.044). In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant (P = 0.048). Cox model analysis of single factor suggested that lymph node status affected the survival rate (P < 0.01), which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with

  4. Paf15 expression correlates with rectal cancer prognosis, cell proliferation and radiation response

    PubMed Central

    Yan, Rong; Zhu, Kun; Dang, Chengxue; Lan, Ke; Wang, Haonan; Yuan, Dawei; Chen, Wei; Meltzer, Stephen J.; Li, Kang

    2016-01-01

    Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response. PMID:27246972

  5. Inflammation-based factors and prognosis in patients with colorectal cancer

    PubMed Central

    Maeda, Kiyoshi; Shibutani, Masatusne; Otani, Hiroshi; Nagahara, Hisashi; Ikeya, Tetsuro; Iseki, Yasuhito; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-01-01

    Several parameters for predicting survival in patients with colorectal cancer have been identified, including the performance status, age, gender and tumor-node-metastasis (TNM) stage. Although the TNM stage is important and useful for predicting the prognosis and determining the appropriate treatment, it is well known that the survival time varies widely, even in patients with the same stage of disease. Therefore, the identification of new parameters capable of more precisely predicting patient survival is needed to help select the optimal treatment, especially in patients in the advanced stage of disease. Although the TNM stage reflects the tumor characteristics, cancer progression and survival are not determined solely based on the local characteristics of the tumor, but also the host systemic immune/inflammatory response. Therefore, using a combination of parameters that reflect both tumor characteristics and the host systemic inflammatory status is thought to be important for accurately predicting patient survival. PMID:26306143

  6. Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

    SciTech Connect

    Kenny, Paraic A.; Bissell, Mina J.

    2005-06-15

    The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

  7. MicroRNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity.

    PubMed

    Hollis, Michael; Nair, Kavitha; Vyas, Arpita; Chaturvedi, Lakshmi Shankar; Gambhir, Sahil; Vyas, Dinesh

    2015-07-21

    Over the past decade, research has shown that aberrant expression of microRNA (miRNA) is involved in colorectal cancer development and progression. MicroRNAs are small sequences of non-coding RNA that regulate expression of genes involved in important cellular functions, such as cell differentiation, multiplication, and apoptosis. A specific miRNA may display the effects of a tumor suppressor or oncogene. Altered miRNA expression is found in colorectal cancer (CRC) and patterns of miRNA expression correlate with CRC detection and outcome. Studies also have examined the use of circulating serum miRNA and fecal miRNA expression as non-invasive markers for early detection. Here, we review recent evidence demonstrating the potential role of miRNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC.

  8. The wisdom of the commons: ensemble tree classifiers for prostate cancer prognosis

    PubMed Central

    Koziol, James A.; Feng, Anne C.; Jia, Zhenyu; Wang, Yipeng; Goodison, Seven; McClelland, Michael; Mercola, Dan

    2009-01-01

    Motivation: Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. Results: Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors. Contact: dmercola@uci.edu PMID:18628288

  9. Differences in the prognosis of early gastric cancer according to sex and age

    PubMed Central

    Suh, Do Dam; Oh, Seong Tae; Yook, Jeong Hwan; Kim, Byung-Sik; Kim, Beom Su

    2016-01-01

    Background: Few studies have compared early gastric cancer (EGC) outcomes according to sex and age. Methods: We retrospectively reviewed 2085 patients who underwent curative gastrectomy for EGC between 1989 and 2000. Prognosis and risk factors for nodal involvement were evaluated according to sex and age. Results: Male sex and age were independent prognostic factors for overall survival (OS) but not relapse-free survival (RFS). In young (⩽55 years) patients, there were no significant differences in RFS and OS between men and women. However, older (>55 years) men had a poorer OS and older women had a poorer RFS. Young female patients had a higher proportion of gastric cancer-related death than young male patients. Female sex was an independent risk factor for nodal involvement in younger patients. Conclusions: Young women with EGC should be more intensively treated and monitored than other patient groups and should not be treated by endoscopic resection. PMID:28203280

  10. Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

    PubMed Central

    Johnson, Ian R.D.; Parkinson-Lawrence, Emma J.; Keegan, Helen; Spillane, Cathy D.; Barry-O'Crowley, Jacqui; Watson, William R.; Selemidis, Stavros; Butler, Lisa M.; O'Leary, John J.; Brooks, Doug A.

    2015-01-01

    Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients. PMID:26473288

  11. Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy.

    PubMed

    Ishikawa, Toshihisa

    2014-01-01

    NF-E2-related factor 2 (NRF2) is a transcription factor that controls the expression of a variety of antioxidant and detoxification genes. Accumulating evidence strongly suggests that NRF2 mediates cancer cell proliferation and drug resistance, as well. Single nucleotide polymorphism (SNP) -617C > A in the anti-oxidant response element-like loci of the human NRF2 gene play a pivotal role in the positive feedback loop of transcriptional activation of the NRF2 gene. Since the SNP (-617A) reportedly decreases the binding affinity to the transcription factors of NRF2/small multiple alignment format (MafK), the homozygous -617A/A allele may attenuate the positive feedback loop of transcriptional activation of the NRF2 gene and reduce the NRF2 protein level. As the consequence, cancer cells are considered to become more sensitive to therapy and less aggressive than cancer cells harboring the -617C (WT) allele. Indeed, Japanese lung cancer patients carrying SNP homozygous alleles (c. -617A/A) exhibited remarkable survival over 1,700 days after surgical operation (log-rank p = 0.021). The genetic polymorphism in the human NRF2 gene is considered as one of prognosis markers for cancer therapy.

  12. G388R mutation of the FGFR4 gene is not relevant to breast cancer prognosis.

    PubMed

    Jézéquel, P; Campion, L; Joalland, M-P; Millour, M; Dravet, F; Classe, J-M; Delecroix, V; Deporte, R; Fumoleau, P; Ricolleau, G

    2004-01-12

    This study screened large cohorts of node-positive and node-negative breast cancer patients to determine whether the G388R mutation of the FGFR4 gene is a useful prognostic marker for breast cancer as reported by Bange et al in 2002. Node-positive (n=139) and node-negative (n=95) breast cancer cohorts selected for mutation screening were followed up for median periods of 89 and 87 months, respectively. PCR - RFLP analysis was modified to facilitate molecular screening. Curves for disease-free survival were plotted according to the Kaplan - Meier method, and a log-rank test was used for comparisons between groups. Three other nonparametric linear rank-tests particularly suitable for investigating possible relations between G388R mutation and early cancer progression were also used. Kaplan - Meier analysis based on any of the four nonparametric linear rank tests performed for node-positive and node-negative patients was not indicative of disease-free survival time. G388R mutation of the FGFR4 gene is not relevant for breast cancer prognosis.

  13. VEGF, Flt-1, and microvessel density in primary tumors as predictive factors of colorectal cancer prognosis

    PubMed Central

    Zygoń, Justyna; Szajewski, Mariusz; Kruszewski, Wiesław Janusz; Rzepko, Robert

    2017-01-01

    Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival. PMID:28357103

  14. Update on triple-negative breast cancer: prognosis and management strategies

    PubMed Central

    Brouckaert, Olivier; Wildiers, Hans; Floris, Giuseppe; Neven, Patrick

    2012-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease comprehending different orphan breast cancers simply defined by the absence of ER/PR/HER-2. Approximately 15%–20% of all breast cancers belong to this phenotype that has distinct risk factors, distinct molecular features, and a particular clinical presentation and outcome. All these features will be discussed in this review. The risk of developing TNBC varies with age, race, genetics, breastfeeding patterns, and parity. Some TNBC are very chemo-sensitive and the majority of patients confronted with and treated for TNBC will never relapse. Some (histological) subgroups of TNBC may have good prognosis even in the absence of chemotherapy. Distinct molecular subgroups within TNBC have been defined now as well. In case metastatic relapse occurs, this is usually within 5 years following surgery, and survival following metastatic relapse is shorter compared to other breast cancer subtypes; treatment options are few and responses lack durability. Novel drug targets and new biomarkers are needed to improve breast cancer care for patients presenting with TNBC. Further molecular/biological unraveling of TNBC is needed. PMID:23071421

  15. Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

    PubMed Central

    Liu, Jie; Song, Bao; Wang, Jia-Lin; Li, Zeng-Jun; Li, Wan-Hu; Wang, Zhe-Hai

    2011-01-01

    AIM: To evaluate the association between of the interleukin-10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS: The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the associations between IL-10 genotypes and the risk of GC. The Kaplan-Meier method with log-rank testing was used to evaluate the association between genotype and survival of the patients. RESULTS: The IL-10 -1082 G allele and GCC (-1082, -819 and -592) haplotype were associated with increased gastric cancer risks (OR 1.2, 95% CI 0.6-3.2, P = 0.007, for -1082 G allele, OR = 2.3, 95% CI, 1.2-4.1, P = 0.005, for GCC haplotype, respectively). However, none of the three IL-10 gene polymorphisms (-1082, -819 and -592) was correlated with gastric cancer survival (P > 0.05), and none of the genotypes of the three IL-10 sites was found as independent prognostic risk factors in the multivariate test. CONCLUSION: IL-10 gene promoter polymorphisms may not be associated with the prognosis of advanced gastric cancer. PMID:21455338

  16. Overexpression of HOXB7 is associated with a poor prognosis in patients with gastric cancer

    PubMed Central

    TU, WEIWEI; ZHU, XINGWU; HAN, YANG; WEN, YUGANG; QIU, GUOQIANG; ZHOU, CHONGZHI

    2015-01-01

    Previous studies have indicated that the homeobox gene HOXB7 is overexpressed in certain cancers, which promotes tumorigenesis. However, less is known about the association between the HOXB7 gene and gastric cancer. The purpose of the present study was to investigate the association between the expression level of HOXB7 and gastric cancer. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of the homeobox B7 (HOXB7) RNA and protein, respectively. In addition, the association between the expression of HOXB7 and the clinicopathological characteristics of gastric cancer was analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate the survival rates, and the COX proportional hazards model was used to investigate univariate and multivariate analyses. The expression level of HOXB7 RNA and protein was significantly elevated in cancerous tissues compared with the corresponding normal mucosa. Increased expression of HOXB7 was significantly associated with tumor size (P=0.01), T stage (P<0.001) and advanced Union for International Cancer Control stage (P=0.003). In addition, patients with positive HOXB7 expression possessed an evident lower overall survival and disease-free survival rate compared with patients with tumors that did not express HOXB7. Furthermore, univariate and multivariate analyses indicated that HOXB7 served as a significant independent prognostic factor for OS and DFS in patients with gastric cancer. The present data indicate that the HOXB7 gene may play an important role in the process of gastric tumorigenesis, and also indicate that HOXB7 may be an important determinant of patient prognosis in gastric cancer. PMID:26722273

  17. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    PubMed

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

  18. Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype

    PubMed Central

    Sun, Xuezheng; Nichols, Hazel B.; Tse, Chiu-Kit; Bell, Mary B.; Robinson, Whitney R.; Sherman, Mark E.; Olshan, Andrew F.; Troester, Melissa A.

    2015-01-01

    Background Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis has received limited attention. Methods Study participants were 1,140 invasive breast cancer patients from Phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer (BC)-specific and overall survival was assessed using Cox proportional hazards models. Results During follow-up (median =13.5 years), 450 patients died, 61% due to breast cancer (n=276). High parity (3+ births) and recent birth (< 5 years before diagnosis) were positively associated with BC-specific mortality, independent of age, race, and selected socioeconomic factors (parity, reference=nulliparous, adjusted hazard ratio [HR]=1.76, 95% confidence interval [CI]=1.13-2.73; birth recency, reference=10+ years, adjusted HR=1.29, 95% CI=0.79, 2.11). The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. Conclusions Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long-term survivors. Impact The biological effects of parity and birth recency may extend from etiology to tumor promotion and progression. PMID:26545404

  19. Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer.

    PubMed

    Cuschieri, K; Brewster, D H; Graham, C; Nicoll, S; Williams, A R W; Murray, G I; Millan, D; Johannessen, I; Hardie, A; Cubie, H A

    2014-12-01

    While much is known about the influence of HPV type on the progression of pre-invasive cervical lesions, the impact of HPV type on cervical cancer prognosis is less evidenced. Thus, we assessed the impact of HPV type on the survival of women diagnosed with cervical cancer. A total of 370 cases of cervical cancer were assessed. Univariate analysis is presented using Kaplan-Meier survival curves and log-rank statistics and multivariable Cox proportional hazard models were generated using age group, socio-economic deprivation, FIGO stage, differentiation and HPV type. HPV grouping was considered in a number of ways with particular reference to the presence or absence of HPV 16 and/or 18. In the univariate analysis, FIGO, age at diagnosis and treatment were associated with poorer survival (p < 0.0001) as was absence of HPV 16 and/or 18 (p = 0.0460). The 25% mortality time in the non-HPV 16/18 vs. HPV16/18 positive group was 615 days and 1,307 days respectively. An unadjusted Cox PH model based HPV16/18 vs. no HPV 16/18 resulted in a hazard ratio of 0.669 (0.450, 0.995). Adjusting for deprivation, FIGO and age group resulted in a hazard ratio of 0.609 (0.395, 0.941) p = 0.025. These data indicate that cancers associated with HPV 16 and/or 18 do not confer worse survival compared to cancers associated with other types, and may indicate improved survival. Consequently, although HPV vaccine is likely to reduce the incidence of cervical cancer it may not indirectly improve cervical cancer survival by reducing the burden of those cancers caused by HPV16/18. © 2014 UICC.

  20. Expression of COL6A1 predicts prognosis in cervical cancer patients.

    PubMed

    Hou, Teng; Tong, Chongjie; Kazobinka, Gallina; Zhang, Weijing; Huang, Xin; Huang, Yongwen; Zhang, Yanna

    2016-01-01

    COL6A1 has been shown to play an important role in tumor initiation and progression. The present study is to investigate the clinical significance of COL6A1 in cervical cancer. In this study, the COL6A1 expression levels in 10 paired cervical cancer tissues and the adjacent non-tumor tissues were examined by real-time PCR. The expression of COL6A1 protein was examined in 162 cervical cancer samples by immunohistochemistry, and the correlation of COL6A1 expression with clinicopathologic factors was analyzed. The overall and recurrent-free survival rates were estimated using Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with multivariate Cox regressions model. The result showed that COL6A1 expression was up-regulated in cervical cancer tissues in compared with that in non-tumor tissues. High expression of COL6A1 was significantly correlated with FIGO stage (P<0.001), tumor size (P=0.025) and lymph node metastasis (P=0.028) of the disease. Moreover, survival analysis showed that high expression of COL6A1 was significantly associated with poorer overall (OS) and recurrent free (RFS) survival (p=0.004 and =0.001, respectively) of cervical cancer patients. Multivariate analysis suggested that COL6A1 expression was an independent prognostic marker of cervical cancer (P=0.029). Thus, COL6A1 may serve as an oncogene in the initiation and progression of cervical cancer, and as a predictor of poor prognosis in cervical cancer patients.

  1. Increased FLI-1 Expression is Associated With Poor Prognosis in Non-Small Cell Lung Cancers.

    PubMed

    Lin, Shiou-Fu; Wu, Chun-Chieh; Chai, Chee-Yin

    2016-09-01

    Friend leukemia integration-1 (FLI-1) antibody, a commercially available antibody directed against the C-terminus of FLI-1 protein-binding domain, has been used as a useful tool in the differential diagnosis of small blue round cell tumors and vascular neoplasms, but shows inconsistent expression in lung cancers. The aims of this study were to evaluate FLI-1 immunohistochemical expression in non-small cell lung cancer (NSCLC), and its relationships between the clinicopathologic parameters and prognosis. We investigated the FLI-1 expression in 108 cases of NSCLC by using multiple tumor microarrays. Correlations between the FLI-1 expression and clinicopathologic parameters and prognostic significance were analyzed. The effect of FLI-1 expression on survival is estimated by Kaplan-Meier survival analysis and Cox proportional hazards models. Our results revealed that patients with high FLI-1 expression had shorter overall survival (P=0.014) than those with low FLI-1 expression. In multivariate analysis, FLI-1 was confirmed as an independent poor prognostic factor in NSCLC (overall survival: hazard ratio, 7.292; 95% confidence interval, 0.294-0.823; P=0.007). In conclusion, this study shows that FLI-1 is expressed variably in different subtypes of NSCLC, and its expression is related to clinicopathologic parameters and poorer prognosis. However, further studies are required to elucidate its function in tumorigenesis of NSCLC.

  2. Tumor apelin, not serum apelin, is associated with the clinical features and prognosis of gastric cancer.

    PubMed

    Feng, Meiyan; Yao, Guodong; Yu, Hongwei; Qing, Yu; Wang, Kuan

    2016-10-12

    To study the association between Apelin expression and the clinical features and postoperative prognosis in patients with gastric cancer (Int J Cancer 136:2388-2401, 2015). Tumor samples and matched adjacent normal tissues were collected from 270 patients with GC receiving surgical resection. The tumor and serum Apelin levels were determined by immunohistochemistry and ELISA methods, respectively. GC cell lines were cultured for migration and invasive assays. Our data showed that tumor Apelin expression status, instead of serum Apelin level, was closely associated with more advance clinical features including tumor differentiation, lymph node and distant metastases. Moreover, patients with high tumor Apelin level had a significantly shorter overall survival period compared to those with low Apelin expression and those with or negative Apelin staining. Our in vitro study revealed that the Apelin regulated the migration and invasion abilities of GC cell lines, accompanied by up-regulations of a variety of cytokines associated with tumor invasiveness. Our data suggest that tumor Apelin can be used as a marker to evaluate clinical characteristics and predict prognosis in GC patients.

  3. CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis

    PubMed Central

    Xin, Xiaoyan; Zeng, Xianqin; Gu, Huajian; Li, Min; Tan, Huaming; Jin, Zhishan; Hua, Teng; Shi, Rui; Wang, Hongbo

    2016-01-01

    CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers. PMID:27608940

  4. Rab27b Is a Potential Predictor for Metastasis and Prognosis in Colorectal Cancer

    PubMed Central

    Bao, Jun; Ni, Yijiang; Qin, Hui; Xu, Li; Ge, Zhijun; Zhan, Feng; Zhu, Huijun; Zhao, Jiabi; Zhou, Xiaoli; Tang, Xiaojun; Tang, Liming

    2014-01-01

    Objective. Rab27b is reported to correlate with cancer development and progression. However, the association between Rab27b expression and the clinical characteristics of colorectal cancer (CRC) is barely investigated. Methods. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113 CRC cases were performed to explore the relationship between Rab27b expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were executed to evaluate the prognosis of CRC. Results. The results demonstrated that the expression levels of Rab27b mRNA and protein were significantly higher in CRC tissues than that in matched noncancerous tissues (P < 0.05). Rab27b protein expression in CRC was statistically correlated with serum CEA level (P = 0.004), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), and TNM stage (P = 0.001). Cox multifactor analysis and Kaplan-Meier method suggested that higher Rab27b protein expression (P = 0.041) and tumor differentiation (P = 0.001) were significantly associated with the overall survival of CRC patients. Conclusions. The data indicated that higher expression of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful predictor of metastasis and prognosis for CRC. PMID:25580113

  5. Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer.

    PubMed

    Kawamata, Futoshi; Kamachi, Hirofumi; Einama, Takahiro; Homma, Shigenori; Tahara, Munenori; Miyazaki, Masaya; Tanaka, Shinya; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru

    2012-12-01

    Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarci-noma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EHBDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.

  6. Convergence of Mutation and Epigenetic Alterations Identifies Common Genes in Cancer That Predict for Poor Prognosis

    PubMed Central

    Chan, Timothy A; Glockner, Sabine; Yi, Joo Mi; Chen, Wei; Van Neste, Leander; Cope, Leslie; Herman, James G; Velculescu, Victor; Schuebel, Kornel E; Ahuja, Nita; Baylin, Stephen B

    2008-01-01

    enabled the discovery of a number of clinically significant genes targeted by multiple modes of inactivation in breast and colon cancer. Importantly, we demonstrate that a subset of these genes predict strongly for poor clinical outcome. Our data define a set of genes that are targeted by both genetic and epigenetic events, predict for clinical prognosis, and are likely fundamentally important for cancer initiation or progression. PMID:18507500

  7. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

    PubMed

    Jing, Jie-Xian; Wang, Yan; Xu, Xiao-Qin; Sun, Ting; Tian, Bao-Guo; Du, Li-Li; Zhao, Xian-Wen; Han, Cun-Zhi

    2014-01-01

    To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

  8. Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

    PubMed Central

    Lan, Xiuwen; Li, Sen; Gao, Hongyu; Nanding, Abiyasi; Quan, Lina; Yang, Chunyan; Ding, Shaohua; Xue, Yingwei

    2017-01-01

    Purpose Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer. Conclusion The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer. PMID

  9. Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome.

    PubMed

    Teltsh, Omri; Porgador, Angel; Rubin, Eitan

    2015-10-20

    Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for interrogation of a cancer immunome and for advancing immune-based prognosis.

  10. Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.

    PubMed

    Nakamura, Hiroe; Nagasaka, Kazunori; Kawana, Kei; Taguchi, Ayumi; Uehara, Yuriko; Yoshida, Mitsuyo; Sato, Masakazu; Nishida, Haruka; Fujimoto, Asaha; Inoue, Tomoko; Adachi, Katsuyuki; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-11-17

    Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer. First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays. Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity. Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.

  11. Decreased xanthine oxidoreductase is a predictor of poor prognosis in early‐stage gastric cancer

    PubMed Central

    Linder, N; Haglund, C; Lundin, M; Nordling, S; Ristimäki, A; Kokkola, A; Mrena, J; Wiksten, J‐P; Lundin, J

    2006-01-01

    Background Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high‐energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. Aim To assess the clinical relevance of XOR expression in gastric cancer. Methods XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease‐specific survival, was assessed. Results XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non‐curative disease, cellular aneuploidy, high S‐phase fraction and high cyclooxygenase‐2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5‐year gastric cancer‐specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I–II (p = 0.01) and lymph node‐negative (p = 0.02) disease, as well as in patients with smaller (⩽5 cm) tumours (p = 0.02). Conclusion XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer. PMID:16935971

  12. Disclosure of cancer diagnosis and prognosis: a survey of the general public's attitudes toward doctors and family holding discretionary powers

    PubMed Central

    Miyata, Hiroaki; Tachimori, Hisateru; Takahashi, Miyako; Saito, Tami; Kai, Ichiro

    2004-01-01

    Background This study aimed to ask a sample of the general population about their preferences regarding doctors holding discretionary powers in relation to disclosing cancer diagnosis and prognosis. Methods The researchers mailed 443 questionnaires to registered voters in a ward of Tokyo which had a socio-demographic profile similar to greater Tokyo's average and received 246 responses (response rate 55.5%). We describe and analysed respondents' attitudes toward doctors and family members holding discretionary powers in relation to cancer diagnoses disclose. Results Amongst respondents who wanted full disclosure about the diagnosis without delay, 117 (69.6 %) respondents agreed to follow the doctor's discretion, whilst 111 (66.1 %) respondents agreed to follow the family member's decision. For respondents who preferred to have the diagnosis and prognosis withheld, 59 (26.5 %) agreed to follow the doctor's decision, and 79 (35.3 %) of respondents agreed with following family member's wishes. Conclusions The greater proportion of respondents wants or permits disclosure of cancer diagnosis and prognosis. In patients who reveal negative attitudes toward being given a cancer disclosure directly, alternative options exist such as telling the family ahead of the patient or having a discussion of the cancer diagnosis with the patient together with the family. It is recommended that health professionals become more aware about the need to provide patients with their cancer diagnosis and prognosis in a variety of ways. PMID:15571636

  13. Psychological effects of a cosmetic education programme in patients with breast cancer.

    PubMed

    Park, H Y; Kim, J H; Choi, S; Kang, E; Oh, S; Kim, J Y; Kim, S W

    2015-07-01

    Treatments for breast cancer often include interventions related to psychosocial issues such as negative body image, loss of femininity, and low self-esteem. We identified the psychological effects of a cosmetics education programme in patients with breast cancer. Cosmetic programme is a specific care designed to help patients handle appearance-related side effects. Thirty-one women with breast cancer at a university hospital in South Korea who received a cosmetics education programme were compared with 29 subjects in a control group who received the treatment as usual. Psychological factors including distress, self-esteem, and sexual functioning were assessed three times (before and after the programme, and at the 1-month follow-up). After the programme, patients in the treatment group were significantly less likely than those in the control group to rely on distress (P = 0.038) and avoidance coping (P < 0.001) but not on self-esteem. The mean scores in the treatment group for sexual functioning were higher than those in the control group after the treatment. Our results suggest the potential usefulness of a brief cosmetics education programme for reducing distress and reliance on negative coping strategies. Implementing a cosmetics programme for patients with breast cancer may encourage patients to control negative psychological factors.

  14. Metabolomic biomarkers of prostate cancer: prediction, diagnosis, progression, prognosis and recurrence

    PubMed Central

    Kelly, Rachel S; Heiden, Matthew Vander; Giovannucci, Edward L; Mucci, Lorelei A

    2016-01-01

    Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodological issues remain to be addressed in order to maximize the utility of metabolomics in the study of prostate cancer. PMID:27197278

  15. [Meta-analysis of relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer].

    PubMed

    Zhang, Xianxiang; Shao, Shihong; Gao, Yuan; Zhang, Maoshen; Lu, Yun

    2016-03-01

    To investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. The literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. There were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05). Extranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer.

  16. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    PubMed Central

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  17. Analysis of the effect of age on the prognosis of breast cancer.

    PubMed

    Cluze, C; Colonna, M; Remontet, L; Poncet, F; Sellier, E; Seigneurin, A; Delafosse, P; Bossard, N

    2009-09-01

    To explore the effect of age at diagnosis on relative survival from breast cancer at different cancer stages and grades, using appropriate statistical modeling of time-varying and non-linear effects of that prognostic covariate. Data on 4,791 female invasive breast cancers diagnosed between 1990 and 1997 were obtained from a French cancer registry. The effect of age on relative survival was studied using an approach based on excess rate modeling. Different models testing non-linear and non-proportional effects of age were explored for each grade and each stage. In the whole population, the effect of age was not linear and varied with the time elapsed since diagnosis. When analyzing the different sub-groups according to grade and stage, age did not have a significant effect on relative survival in grade 1 or stage 3 tumors. In grade 2 and stage 4 tumors, the excess mortality rate increased with age, in a linear way. In grade 3 tumors, age was a time-dependent factor: older women had higher excess rates than younger ones during the first year after diagnosis whereas the inverse phenomenon was observed 5 years after diagnosis. Our findings suggest that when taking into account grade and stage, the time-varying impact of young age at diagnosis is limited to grade 3 tumors, without evidence of worst prognosis at 5 years for the youngest women.

  18. Methylated circulating tumor DNA in blood: power in cancer prognosis and response

    PubMed Central

    Warton, Kristina; Mahon, Kate L; Samimi, Goli

    2016-01-01

    Circulating tumor DNA (ctDNA) in the plasma or serum of cancer patients provides an opportunity for non-invasive sampling of tumor DNA. This ‘liquid biopsy’ allows for interrogations of DNA such as quantity, chromosomal alterations, sequence mutations and epigenetic changes, and can be used to guide and improve treatment throughout the course of the disease. This tremendous potential for real-time ‘tracking’ in a cancer patient has led to substantial research efforts in the ctDNA field. ctDNA can be distinguished from non-tumor DNA by the presence of tumor-specific mutations and copy number variations, and also by aberrant DNA methylation, with both DNA sequence and methylation changes corresponding to those found in the tumor. Aberrant methylation of specific promoter regions can be a very consistent feature of cancer, in contrast to mutations, which typically occur at a wide range of sites. This consistency makes ctDNA methylation amenable to the design of widely applicable clinical assays. In this review, we examine ctDNA methylation in the context of monitoring disease status, treatment response and determining the prognosis of cancer patients. PMID:26764421

  19. Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer

    PubMed Central

    Pickard, Mark R; Green, Andrew R; Ellis, Ian O; Caldas, Carlos; Hedge, Vanessa L; Mourtada-Maarabouni, Mirna; Williams, Gwyn T

    2009-01-01

    -translational modification (by Fau and MELK) rather than the rate of transcription of Bcl-G itself. Conclusions The combination of in vitro functional studies with the analysis of gene expression in clinical breast cancer samples indicates that three functionally interconnected genes, Fau, Bcl-G and MELK, are crucially important in breast cancer and identifies them as attractive targets for improvements in breast cancer risk prediction, prognosis and therapy. PMID:19671159

  20. Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer.

    PubMed

    Pickard, Mark R; Green, Andrew R; Ellis, Ian O; Caldas, Carlos; Hedge, Vanessa L; Mourtada-Maarabouni, Mirna; Williams, Gwyn T

    2009-01-01

    the rate of transcription of Bcl-G itself. The combination of in vitro functional studies with the analysis of gene expression in clinical breast cancer samples indicates that three functionally interconnected genes, Fau, Bcl-G and MELK, are crucially important in breast cancer and identifies them as attractive targets for improvements in breast cancer risk prediction, prognosis and therapy.

  1. Impact of Sulfatase-2 on cancer progression and prognosis in patients with renal cell carcinoma.

    PubMed

    Kumagai, Shin; Ishibashi, Kei; Kataoka, Masao; Oguro, Toshiki; Kiko, Yuichirou; Yanagida, Tomohiko; Aikawa, Ken; Kojima, Yoshiyuki

    2016-11-01

    Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCC and low SULF-2 RCC were 100% and 71.4%, respectively (log-rank P = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCC with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling.

  2. Platelet-lymphocyte ratio acts as an indicator of poor prognosis in patients with breast cancer

    PubMed Central

    Sun, Qiong; Qin, Boyu; Zhao, Weihong; Yang, Junlan

    2017-01-01

    Platelet-lymphocyte ratio (PLR) is a hematological parameter which is investigated as a biomarker for prognosis in patients with breast cancer. Due to the controversial results from previous studies, we performed a meta-analysis. Databases of PubMed, Embase and Web of Science were searched to identify eligible studies. STATA version 12.0 was used for statistical analysis. Seven studies with 3,741 patients were ultimately included in this meta-analysis. High PLR was associated with poor overall survival (OS) (HR = 1.55, 95% CI = 1.07–2.25, p = 0.022) and disease-free survival (DFS) (HR = 1.73, 95% CI = 1.3-2.3, p < 0.001) in breast cancer patients. Subgroup analyses disclosed that elevated PLR could predict worse OS in Asian populations and poor DFS in both Asian and non-Asian patients. In addition, PLR remains a significant prognostic marker for OS in patients receiving systemic treatment (HR = 1.78, 95% CI = 1.06–2.99, p = 0.03) and patients receiving chemotherapy (HR = 2.82, 95% CI = 1.09–7.26, p = 0.032). High PLR also indicates poor DFS in patients who receive chemotherapy (HR = 2.6, 95% CI = 1.47–4.61, p = 0.001), surgery (HR = 1.8, 95% CI = 1.12–2.89, p = 0.016) and systemic treatment (HR = 2.03, 95% CI = 1.03–4.01, p = 0.042). Moreover, PLR was also in association with HER-2 positivity (OR = 1.48, 95% CI = 1.2–1.83, p < 0.001). In conclusion, this meta-analysis revealed that PLR could serve as an indicator of poor prognosis in patients with breast cancer. PMID:27906679

  3. Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer.

    PubMed

    Zhang, Li; Wang, Hua; Tian, Lin; Li, Haixia

    2016-07-01

    Epithelial ovarian cancer (EOC) is one of the worst malignancies in females with poor overall survival due to the rapid metastasis and the absence of ideal biomarkers. Ubiquitin-specific protease 7 (USP7), an important deubiquitinating enzyme, was reported to be upregulated in several cancers, including liver, prostate and colon cancers. Membrane associated RING-CH protein 7 (MARCH7) belongs to the member of the E3 ubiquitin ligases. In addition, MARCH7 regulates T cell proliferation and the neuronal development and participates in the membrane trafficking and protein degradation. Importantly, MARCH7 itself is ubiquitinated and acts as a potential substrate of USP7. However, the roles of USP7 and MARCH7 in EOC remain to be investigated. We collected 121 EOC patients and analyzed the expression levels of USP7 and MARCH7 in tumor tissues with immunohistochemical staining. We found that the high expression of the two proteins was correlated with lymph node metastasis in EOC patients. Univariate and multivariate analyses revealed that the patients with high expression of the two proteins showed poorer prognosis compared with other patients. Subsequently, using SKOV3 human ovarian adenocarcinoma cells, we showed that either USP7 or MARCH7 enhanced the proliferation and invasion abilities. Moreover, USP7 could regulate the expression levels of E-cadherin and β-catenin through the MARCH7 signaling pathway. Our findings indicate that USP7 and MARCH7 are involved in the progression of EOC. In conclusion, analyzing the expression of USP7 and MARCH7 has high prognostic value in predicting EOC prognosis.

  4. Should cancer patients be informed about their diagnosis and prognosis? Future doctors and lawyers differ

    PubMed Central

    Elger, B; Harding, T

    2002-01-01

    Setting and design: Anonymous questionnaires were distributed to convenience samples of students at the University of Geneva containing four vignettes describing a cancer patient who wishes, or alternatively, who does not wish to be told the truth. Participants: One hundred and twenty seven medical students and 168 law students. Main outcome measures: Five point Likert scale of responses to the vignettes ranging from "certainly inform" to "certainly not inform" the patient. Results: All medical students and 96% of law students favoured information about the diagnosis of cancer if the patient requests it. Seventy four per cent of medical students and 82% of law students favoured informing a cancer patient about his or her prognosis (p = 0.0003). Thirty five per cent of law students and 11.7% of medical students favoured telling about the diagnosis (p = 0.0004) and 25.6% of law students and 7% of medical students favoured telling about the prognosis (p < 0.0001) even if the patient had clearly expressed his wish not to be informed. Law students indicated significantly more often than medical students reasons to do with the patient's good, legal obligations, and the physician's obligation to tell the truth, and significantly less often than medical students that their attitude had been determined predominantly by respect for the autonomous choice of the patient. Conclusion: Differences in attitudes according to the type of case and the type of studies were related to convictions about the benefit or harm to the patient caused by being given information. The self reported reasons of future physicians and future lawyers are helpful when considering means to achieve a better acceptance of patients' right to know and not to know. PMID:12161583

  5. Oral cancer prognosis based on clinicopathologic and genomic markers using a hybrid of feature selection and machine learning methods

    PubMed Central

    2013-01-01

    Background Machine learning techniques are becoming useful as an alternative approach to conventional medical diagnosis or prognosis as they are good for handling noisy and incomplete data, and significant results can be attained despite a small sample size. Traditionally, clinicians make prognostic decisions based on clinicopathologic markers. However, it is not easy for the most skilful clinician to come out with an accurate prognosis by using these markers alone. Thus, there is a need to use genomic markers to improve the accuracy of prognosis. The main aim of this research is to apply a hybrid of feature selection and machine learning methods in oral cancer prognosis based on the parameters of the correlation of clinicopathologic and genomic markers. Results In the first stage of this research, five feature selection methods have been proposed and experimented on the oral cancer prognosis dataset. In the second stage, the model with the features selected from each feature selection methods are tested on the proposed classifiers. Four types of classifiers are chosen; these are namely, ANFIS, artificial neural network, support vector machine and logistic regression. A k-fold cross-validation is implemented on all types of classifiers due to the small sample size. The hybrid model of ReliefF-GA-ANFIS with 3-input features of drink, invasion and p63 achieved the best accuracy (accuracy = 93.81%; AUC = 0.90) for the oral cancer prognosis. Conclusions The results revealed that the prognosis is superior with the presence of both clinicopathologic and genomic markers. The selected features can be investigated further to validate the potential of becoming as significant prognostic signature in the oral cancer studies. PMID:23725313

  6. Association of smoking status with prognosis in bladder cancer: A meta-analysis

    PubMed Central

    Dai, Meng; Chen, Pengliang; Zhao, Hongfan; Wei, Qiang; Li, Fei; Tan, Wanlong

    2017-01-01

    There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05–1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings. PMID:27902481

  7. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis.

    PubMed

    Gu, Lihu; Chen, Manman; Guo, Dongyu; Zhu, Hepan; Zhang, Wenchao; Pan, Junhai; Zhong, Xin; Li, Xinlong; Qian, Haoran; Wang, Xianfa

    2017-01-01

    The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library. The baseline information extracted were: authors, year of publication, country where the study was performed, study design, sample size, follow-up time, baseline characteristics of the study population, pathologic data, overall survival (OS). A total of 15 eligible studies covering 3291 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The analysis showed that the expression level of PD-L1 was associated with the overall survival in GC (Hazard Ratio, HR = 1.46, 95%CI = 1.08-1.98, P = 0.01, random-effect). In addition to the above, subgroup analysis showed that GC patients with deeper tumor infiltration, positive lymph-node metastasis, positive venous invasion, Epstein-Barr virus infection positive (EBV+), Microsatellite Instability (MSI) are more likely to expression PD-L1. The results of this meta-analysis suggest that GC patients, specifically EBV+ and MSI, may be prime candidates for PD-1 directed therapy. These findings support anti-PD-L1/PD-1 antibodies as a kind of immunotherapy which is promising for GC.

  8. Elevated RABEX-5 protein expression predicts poor prognosis in combined small cell lung cancer.

    PubMed

    Zhang, Fuliang; Zhang, Meng; Hu, Guohua; Cai, Qiling; Xu, Tongbai

    2015-11-01

    RABEX-5 has been studied in various solid tumors, but its role in combined small cell lung cancer (C-SCLC) remains unknown. This study aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with C-SCLC. Fifty-two C-SCLC patients who received radical surgery were enrolled in our study. The clinicalpathological data and survival time were reviewed. The mRNA and protein expression of RABEX-5 from the paired tumor tissues and adjacent normal tissues were determined, and its relationship with clinicalpathological variables and prognosis was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of RABEX-5 for C-SCLC. The mRNA and protein expression level of RABEX-5 was significantly elevated in C-SCLC tissues. The increased RABEX-5 protein expression was correlated with clinical stage (p = 0.011) and tumor recurrence (p = 0.006). The median OS and DFS was significantly shorter in the high RABEX-5 expression group compared to low RABEX-5 expression group (OS: 12.0 vs. 21.7 months, p = 0.014; DFS: 6.7 vs. 11.8 months, p = 0.005). Multivariate Cox analysis indicated that high RABEX-5 protein expression was an independent prognostic factor for OS and DFS (p < 0.001). RABEX-5 is a potential useful indicator and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients.

  9. Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer

    PubMed Central

    Chen, Mei-Jyh; Chen, Chien-Chuan; Kuo, Sung-Hsin; Lai, I-Rue; Yeh, Kun-Huei; Lin, Ming-Tsan; Wang, Hsiu-Po; Cheng, Ann-Lii; Lin, Jaw-Town; Shun, Chia-Tung; Wu, Ming-Shiang

    2017-01-01

    Background Whether the characteristics and prognosis of gastric cancer (GC) are different in patients with and without Helicobacter pylori (HP) remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions. Methods From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG) I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients. Results We found four characteristics of HP negative GC in comparison to HP positive GC: (1) higher proportion of the proximal tumor location (24.0%, P = 0.004), (2) more diffuse histologic type (56.1%, p = 0.008), (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV disease (40.6%, p = 0.03). Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035). In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04–1.71, p = 0.019) in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05–2.51,p = 0.026). Conclusion We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor. PMID:28152027

  10. Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer.

    PubMed

    Li, Quan; Jin, Wenxu; Cai, Yefeng; Yang, Fang; Chen, Endong; Ye, Danrong; Wang, Qingxuan; Guan, Xiaoxiang

    2017-04-08

    Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Therefore, finding a novel molecular biomarker for TNBC to achieve target therapy and predict its prognosis is crucial in preventing inappropriate treatment. Regulator of G-protein signaling (RGS) families of protein can negatively regulate signaling of heterotrimeric G proteins and are known to be upregulated in various tumors. In this study, we demonstrated that RGS20 was more highly expressed in TNBC tumor tissue than in adjacent normal tissue by analyzing the cancer genome atlas (TCGA) database. However, RGS20 expression was low in all breast cancer and luminal breast cancer patients. Validated by the TCGA cohort, RGS20 was upregulated in lymph node-positive TNBC compared with that in lymph node-negative breast cancer. High expression of RGS20 had a risk of lymph node metastasis, ki-67 > 14%, poor N stage, and poor clinical stage in the immunohistochemistry of tissue microarrays. Moreover, K-M plot analysis showed that TNBC patients with high RGS20 expression had poor relapse-free survival. In summary, the findings revealed that RGS20 was a special TNBC oncogene that promoted tumor progression and influenced TNBC prognosis. This study is the first to show that RGS20 was a special oncogene, and its high expression was significantly associated with the progression and prognosis of TNBC. RGS20 may be a novel molecular biomarker for the targeted therapy and prognosis of TNBC.

  11. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

    PubMed

    Filella, Xavier; Foj, Laura

    2016-10-26

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

  12. Association of miR-21 with esophageal cancer prognosis: a meta-analysis.

    PubMed

    Wen, S-W; Zhang, Y-F; Li, Y; Liu, Z-X; Lv, H-L; Li, Z-H; Xu, Y-Z; Zhu, Y-G; Tian, Z-Q

    2015-06-12

    The present study aimed to explore the relationship between miRNA expression and survival in patients with esophageal cancer (EC) using meta-analysis. We searched PubMed, EMBASE, CNKI, Wanfang, and ISI Web of Science databases without time restrictions, and extracted relevant data, such as the name of first author, publication year, age, gender, number of case, etc. from the studies included. We calculated the pooled hazard ratios (HRs) using the RevMan 5.2 software. A total of five studies involving 504 subjects were included in the meta-analysis, with the purpose of analyzing the association of miRNA-21 expression with EC prognosis. The pooled HR of elevated versus decreased miR-21 expression in EC was 1.87 [95% confidence interval (CI): 1.37-2.55, P < 0.001], with elevated miR-21 expression being associated with poorer prognosis for patients with EC. Our results support a prognostic role for miR-21 in EC.

  13. Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

    PubMed Central

    KURATA, KENTO; ONODA, NAOYOSHI; NODA, SATORU; KASHIWAGI, SHINICHIRO; ASANO, YUKA; KAWAJIRI, HIDEMI; TAKASHIMA, TSUTOMU; TANAKA, SAYAKA; OHSAWA, MASAHIKO; HIRAKAWA, KOSEI

    2015-01-01

    The protein nestin, a neuronal stem cell marker, has been reported to indicate a poor prognosis in various tumours. Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its molecular background has not been identified. The present study evaluated the expression of nestin and its significance in ATC. Tissue samples from 23 patients with ATC were subjected to immunohistochemical staining and the staining intensity of nestin in the cytoplasm was evaluated. The expression of nestin in the tumour cytoplasm was confirmed in 6 of the 23 tissue samples (26.1%). Between the nestin-positive group (n=6) and the nestin-negative group (n=17), there were no significant differences in the clinicopathological factors of the patients. However, the nestin-positive group exhibited significantly worse prognoses than the nestin-negative group (median survival time, 86.5 vs. 306 days; P<0.01, log-rank test). The multivariate analysis indicated that nestin expression was a prognostic indicator for the ATC patients (hazard ratio, 5.59; 95% confidence interval, 1.63–19.50; P<0.01), which is independent of the known clinical indicators. Nestin expression has the potential to be an independent indicator of a poor prognosis for patients with ATC. PMID:26622582

  14. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers

    PubMed Central

    Filella, Xavier; Foj, Laura

    2016-01-01

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. PMID:27792187

  15. Comparison of prognosis and clinical features between synchronous bilateral and unilateral breast cancers.

    PubMed

    Karakas, Yusuf; Kertmen, Neyran; Lacin, Sahin; Aslan, Alma; Demir, Metin; Ates, Ozturk; Aksoy, Sercan; Altundag, Kadri

    2017-01-01

    The clinical significance of synchronous bilateral breast cancer (SBBC) is unclear and its influence on prognosis is controversial. Our study objective was to determine the epidemiological features, tumor characteristics, and prognosis of SBBC in comparison with those of unilateral breast cancer (UBC). A total of 3675 breast cancer patients diagnosed and treated between 2000 and 2014 were evaluated. Of these patients, 132 (3.6%) had bilateral breast cancer, including 55 patients (1.5%) with SBBC and 77 (2.1%) with metachronous bilateral breast cancer (MBBC). The patient demographic characteristics, including survival data and clinicopathological tumor characteristics, were obtained from medical charts and compared between the patients with SBBC and those with UBC. The median age in the SBBC group was 51 years (range 32-77). The mastectomy rate was higher in the SBBC group (72.7%) than in the UBC group (66.6%) (p=0.08). In both the SBBC and UBC groups, the baseline clinicopathological features and the history of treatment with radiotherapy and chemotherapy were similar. Infiltrating ductal carcinoma was the most common histology in both groups. Lobular histology was more frequent in the SBBC group (36.3%) than in the UBC group (17.1%; p<0.001). Stage IV disease at initial presentation was more frequent in the SBBC group than in the UBC group (34.5 vs 8.7%, p<0.001). The 5-year disease-free survival (DFS) rates were 90% and 82% in the SBBC and UBC groups, respectively (p=0.99). The 5-year overall survival (OS) rates were 83% and 88%, respectively (p=0.357). The multivariate Cox regression analysis, including stage, hormone receptor status, grade, and SBBC, revealed that the presence of SBBC was not associated with OS (hazard ratio 0.929; 95% confidence interval, 0.455-0.1894, p=0.839). Despite the differences in histology, initial stage, and other characteristics, the prognoses of UBC and SBBC were similar.

  16. Protein Interaction Network Underpins Concordant Prognosis Among Heterogeneous Breast Cancer Signatures

    PubMed Central

    Chen, James; Sam, Lee; Huang, Yong; Lee, Younghee; Li, Jianrong; Liu, Yang; Xing, H. Rosie; Lussier, Yves A.

    2010-01-01

    Characterizing the biomolecular systems’ properties underpinning prognosis signatures derived from gene expression profiles remains a key clinical and biological challenge. In breast cancer, while different “poor-prognosis” sets of genes have predicted patient survival outcome equally well in independent cohorts, these prognostic signatures have surprisingly little genetic overlap. We examine ten such published expression-based signatures that are predictors or distinct breast cancer phenotypes, uncover their mechanistic interconnectivity through a protein-protein interaction network, and introduce a novel cross-“gene expression signature” analysis method using (i) domain knowledge to constrain multiple comparisons in a mechanistically relevant single-gene network interactions, and (ii) scale-free permutation resampling to statistically control for hubness (SPAN - Single Protein Analysis of Network with constant node degree per protein). At adjusted p-values < 5%, 54 genes thus identified have a significantly greater connectivity than those through meticulous permutation resampling of the context-constrained network. More importantly, eight of ten genetically non-overlapping signatures are connected through well-established mechanisms of breast cancer oncogenesis and progression. Gene Ontology enrichment studies demonstrate common markers of cell cycle regulation. Kaplan-Meier analysis of three independent historical gene expression sets confirms this network-signature’s inherent ability to identify “poor outcome” in ER(+) patients without the requirement of machine learning. We provide a novel demonstration that genetically distinct prognosis signatures, developed from independent clinical datasets, occupy overlapping prognostic space of breast cancer via shared mechanisms that are mediated by genetically different yet mechanistically comparable interactions among proteins of differentially expressed genes in the signatures. This is the first study

  17. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    PubMed Central

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David

    2015-01-01

    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  18. Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers.

    PubMed

    Jonasson, Jon G; Stefansson, Olafur A; Johannsson, Oskar T; Sigurdsson, Helgi; Agnarsson, Bjarni A; Olafsdottir, Gudridur H; Alexiusdottir, Kristin K; Stefansdottir, Hrefna; Munoz Mitev, Rodrigo; Olafsdottir, Katrin; Olafsdottir, Kristrun; Arason, Adalgeir; Stefansdottir, Vigdis; Olafsdottir, Elinborg J; Barkardottir, Rosa B; Eyfjord, Jorunn E; Narod, Steven A; Tryggvadóttir, Laufey

    2016-09-27

    The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers. We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012. Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03). Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

  19. The Trend of Age-Group Effect on Prognosis in Differentiated Thyroid Cancer.

    PubMed

    Shi, Rong-Liang; Qu, Ning; Liao, Tian; Wei, Wen-Jun; Wang, Yu-Long; Ji, Qing-Hai

    2016-06-08

    Age has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox models were built to analyze the outcomes and risk factors. Increasing age gradient with a 10-year interval was associated with the trend of higher proportions for male gender, grade III/IV and summary stage of distant metastases. Both CSS and OS continued to worsen with increasing age, being poorest in in the oldest age group (≥71); multivariate analysis confirmed that CSS continued to fall with each age decade, significantly starting at 60 years (HR = 7.5, 95% 1.0-54.1, p = 0.047) compared to the young group (≤20). Similarly, multivariate analysis suggested that OS continued worsening with increasing age, but starting at 40 years (HR = 3.7, 95% 1.4-10.1, p = 0.009) compared to the young group. The current study suggests that an age exceeding 60 years itself represents an unfavorable prognostic factor and high risk for cancer-specific death in DTC.

  20. Cancer Stem Cells: A systems biology view of their role in prognosis and therapy

    PubMed Central

    Mertins, Susan D.

    2014-01-01

    Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSC). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of cancer stem cells can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes. PMID:24418909

  1. Incidence, predictive factors, and prognosis for winged scapula in breast cancer patients after axillary dissection.

    PubMed

    Nevola Teixeira, Luiz Felipe; Lohsiriwat, Visnu; Schorr, Mario Casales; Luini, Alberto; Galimberti, Viviana; Rietjens, Mario; Garusi, Cristina; Gandini, Sara; Sarian, Luis Otavio Zanatta; Sandrin, Fabio; Simoncini, Maria Claudia; Veronesi, Paolo

    2014-06-01

    Axillary lymph node dissection is part of breast cancer surgery, and winged scapula is a possible sequela. Data regarding its incidence, predictive factors, and patient prognosis remains inconsistent. Ignorance of its diagnosis may lead to undertreatment with physical morbidity. Breast cancer patients with axillary lymph node dissection were prospectively recruited. Postoperative examinations by the physiotherapy staff were performed. One hundred eighty-seven patients were recruited during July-October 2012; 51 patients had a positive diagnosis (27.2 %), with 38 patients (86 %) who recovered completely from the winged scapula, while 6 patients (13 %) still had winged scapula at 6 months after surgery. One hundred thirty patients underwent mastectomy and 100 cases had immediate reconstruction. Age, BMI, previous shoulder joint morbidity, and breast surgery were not associated with winged scapula. Neoadjuvant treatment, mastectomy or conservative surgery, immediate reconstruction, tumor size, and nodal involvement also did not show any correlation. Breast reconstruction with prosthesis, even with serratus muscle dissection, does not increase the incidence of winged scapula. Winged scapula is not an uncommon incidence after breast cancer surgery. Physiotherapy is related to the complete recovery. The severity or grading of the winged scapula and the recovery time after physiotherapy should be investigated in the future studies.

  2. Survival prognosis and variable selection: A case study for metastatic castrate resistant prostate cancer patients

    PubMed Central

    Wengel Mogensen, Søren; H. Petersen, Anne; Buchardt, Ann-Sophie; Hansen, Niels Richard

    2016-01-01

    Survival prognosis is challenging, and accurate prediction of individual survival times is often very difficult. Better statistical methodology and more data can help improve the prognostic models, but it is important that methods and data usages are evaluated properly. The Prostate Cancer DREAM Challenge offered a framework for training and blinded validation of prognostic models using a large and rich dataset on patients diagnosed with metastatic castrate resistant prostate cancer. Using the Prostate Cancer DREAM Challenge data we investigated and compared an array of methods combining imputation techniques of missing values for prognostic variables with tree-based and lasso-based variable selection and model fitting methods. The benchmark metric used was integrated AUC (iAUC), and all methods were benchmarked using cross-validation on the training data as well as via the blinded validation. We found that survival forests without prior variable selection achieved the best overall performance (cv-iAUC = 0.70, validation-iACU = 0.78), while a generalized additive model was best among those methods that used explicit prior variable selection (cv-iAUC = 0.69, validation-iACU = 0.76). Our findings largely concurred with previous results in terms of the choice of important prognostic variables, though we did not find the level of prostate specific antigen to have prognostic value given the other variables included in the data. PMID:28105311

  3. Association of Vasculogenic Mimicry Formation and CD133 Expression with Poor Prognosis in Ovarian Cancer.

    PubMed

    Liang, Jun; Yang, Bo; Cao, Qinying; Wu, Xiaohua

    2016-01-01

    This study was conducted to investigate the association of vasculogenic mimicry (VM) formation and CD133 expression with the clinical outcomes of patients with ovarian cancer. This retrospective study was performed in 120 ovarian carcinoma samples. VM formation and CD133 expression was identified with CD31/periodic acid-Schiff double-staining and CD133 immunohistochemical staining. Collected clinical and pathological data included age at diagnosis, histologic type, tumor grade, tumor stage, lymph node metastases and response to chemotherapy. The overall survival time was calculated. VM was identified in 52 (43%) of 120 ovarian carcinoma tissues and CD133 expression was found in 56 (47%) cases. Both VM formation and CD133 expression were associated with advanced tumor stage, high-grade carcinoma and non-response to chemotherapy (p < 0.05). They were also associated with shorter overall survival time (p < 0.05) by log-rank test. Combined marker of VM formation and CD133 expression was associated with high-grade ovarian carcinoma, late-stage disease, non-response to chemotherapy and shorter overall survival time (p < 0.05). VM formation and CD133 expression can provide additional prognostic information for patients with ovarian cancer. Combined marker of VM formation and CD133 expression may be a potent predictor for poor prognosis for patients with ovarian cancer. © 2016 S. Karger AG, Basel.

  4. High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer.

    PubMed

    Zhang, Song; Zhang, Dong; Gong, Mingfu; Wen, Li; Liao, Cuiwei; Zou, Liguang

    2017-05-17

    Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain. Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer. Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free survival and 2.88 (2.07-4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total. Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.

  5. Prognosis Prediction for Postoperative Esophageal Cancer Patients Using Onodera's Prognostic Nutritional Index.

    PubMed

    Matsumoto, Hideo; Okamoto, Yuko; Kawai, Akimasa; Ueno, Daisuke; Kubota, Hisako; Murakami, Haruaki; Higashida, Masaharu; Hirai, Toshihiro

    2017-07-20

    Preoperative nutritional status may impact surgical outcome and prognosis. We evaluated the predictive value of Onodera's prognostic nutritional index (O's-PNI) of surgical outcome following esophagectomy in esophageal cancer patients. In total, 144 patients undergoing esophagectomy for esophageal cancer from April 2010 to May 2015 were evaluated, retrospectively. Eighty-four patients were enrolled in this study. O's-PNIs were calculated before surgery, discharge, and 1, 2, and 6 mo after discharge. The relationship between O's-PNI and occurrence of complications as classified by the Clavien-Dindo (C-D) classification, length of hospital stay, and survival time was investigated. The mean O's-PNI for patients with complications of more than Grade 2 by the C-D classification was 37.4, which was significantly lower than that for Grades 0 or 1 (40.5, P = 0.0094). A negative correlation was obtained between O's-PNI and hospital stay length (P = 0.0006), whereas a positive correlation was obtained for O's-PNI at 6 mo postsurgery and overall survival (P = 0.0171, P = 0.0201). O's-PNI may represent a useful indicator of the occurrence of complications and length of hospital stay, and may influence overall survival at 6 mo postsurgery. Nutritional management during the perioperative period could therefore contribute to satisfactory outcomes following esophagectomy in esophageal cancer patients.

  6. MicroRNAs as Biomarkers for Diagnosis, Prognosis and Theranostics in Prostate Cancer

    PubMed Central

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2016-01-01

    Prostate cancer (PC) includes several phenotypes, from indolent to highly aggressive cancer. Actual diagnostic and prognostic tools have several limitations, and there is a need for new biomarkers to stratify patients and assign them optimal therapies by taking into account potential genetic and epigenetic differences. MicroRNAs (miRNAs) are small sequences of non-coding RNA regulating specific genes involved in the onset and development of PC. Stable miRNAs have been found in biofluids, such as serum and plasma; thus, the measurement of PC-associated miRNAs is emerging as a non-invasive tool for PC detection and monitoring. In this study, we conduct an in-depth literature review focusing on miRNAs that may contribute to the diagnosis and prognosis of PC. The role of miRNAs as a potential theranostic tool in PC is discussed. Using a meta-analysis approach, we found a group of 29 miRNAs with diagnostic properties and a group of seven miRNAs with prognostic properties, which were found already expressed in both biofluids and PC tissues. We tested the two miRNA groups on The Cancer Genome Atlas dataset of PC tissue samples with a machine-learning approach. Our results suggest that these 29 miRNAs should be considered as potential panel of biomarkers for the diagnosis of PC, both as in vivo non-invasive test and ex vivo confirmation test. PMID:27011184

  7. Biliary metastasis in colorectal cancer confers a poor prognosis: case study of 5 consecutive patients

    PubMed Central

    Koh, Frederick Hong-Xiang; Shi, Wang

    2017-01-01

    The biliary duct is an extremely rare site for colon cancer metastasis. It often leads to a diagnostic dilemma, since primary cholangiocarcinoma (potentially treatable with surgery) has a similar presentation. This paper highlights our experience with 5 consecutive patients who had colon malignancy with biliary metastasis, and prognosis of their disease. Five patients, with a history of primary colon cancer since 2010, were identified to have biliary metastasis. Of these, 4 (80.0%) patients were male. The median time to diagnosis of biliary metastasis from diagnosis of colon cancer was 59.2 months (0-70.1 months), and all exhibited symptoms of biliary obstruction or its associated complications. Evaluation of the tumour samples revealed all specimens to be negative for CK7 but positive for CK20, suggestive of a colorectal primary. The median survival of the 5 patients was 23.5 months (1.8-44.5 months) from the diagnosis of biliary metastasis. However, none of their death was related to the direct complication of biliary obstruction. Biliary metastasis is a rare entity for metastatic colon malignancy. Diagnosis may be difficult radiologically, and immunohistochemical staining may help in identification. The overall survival for these patients is dismal. PMID:28317047

  8. Expression of Adiponectin Receptor-1 and Prognosis of Epithelial Ovarian Cancer Patients

    PubMed Central

    Li, Xiahui; Yu, Zhe; Fang, Liping; Liu, Fang; Jiang, Kui

    2017-01-01

    Background Adiponectin receptor-1 (AdipoR1) has been reported to be associated with the risk of obesity-associated malignancies, including epithelial ovarian cancer (EOC). The aim of this study was to determine if AdipoR1 could serve as a prognosis indicator for patients with EOC. Material/Methods In this study, expression of AdipoR1 in 73 EOC patients consecutively admitted to our hospital was detected by immunohistochemical staining. Univariate and multivariate analyses were performed to assess the relationship between AdipoR1 expression level and progression-free survival (PFS) and overall survival (OS) rates in patients. Results A relatively lower expression of AdipoR1 in the cancerous tissues was detected compared to normal ovarian tissues, but the difference was not significant (p>0.05). AdipoR1 expression level in EOC patients was negatively correlated with advanced FIGO stages in patients and tumor differentiation, but had no correlation with pathological types, presenting of ascites, shorter platinum-free interval (PFI), diabetes, preoperative and postoperative body mass index (BMI), or platelet counts (p>0.05). Moreover, patients with AdipoR1 expression had a significantly longer PFS and OS compared to the negative expression group (p<0.001). Conclusions Our findings suggest that AdipoR1 expression level in cancerous tissues might serve as an independent prognostic indicator in EOC patients and is associated with longer PFS and OS. PMID:28356549

  9. Information given to cancer patients on diagnosis, prognosis and treatment: the clinical oncologist's perspective.

    PubMed

    Belvedere, Ornella; Minisini, Alessandro; Ramello, Monica; Sobrero, Alberto; Grossi, Francesco

    2004-08-01

    The extent of information to cancer patients is, in general, culture-dependent. Information mainly refers to three aspects, namely diagnosis (Dx), prognosis (Px) and treatment (Rx), but the relative contribution of each domain to the information given overall is not available. To address this issue, we e-mailed a questionnaire to 9893 members of the American Society of Clinical Oncology (ASCO) asking whether they agree that information about Dx, Px and Rx contribute differently to the information given to the cancer patient overall and, if so, to what extent, both in the adjuvant and advanced settings. 857 questionnaires were evaluable. There was no statistically significant difference between the contribution of these 3 domains in the adjuvant setting (33%, 34% and 33%, respectively). In subgroup analysis, medical oncologists and haematologists attributed a significantly higher contribution of Px information compared with other specialists (P < 0.05). In the advanced setting, respondents estimated a higher contribution of Px (41%) to patient information overall compared with Dx and Rx (28% and 31%, respectively; P < 0.05). This finding was more pronounced in North America than in Europe (P < 0.0001), and in Germanic-language than in Romance-language countries (P = 0.005). In conclusion, information on Dx, Px and Rx are believed to contribute differently to the information delivered to cancer patients overall, depending on the stage of disease, the cultural environment and the specialty of the physician.

  10. Cervical cancer screening in Europe: Quality assurance and organisation of programmes.

    PubMed

    Elfström, K Miriam; Arnheim-Dahlström, Lisen; von Karsa, Lawrence; Dillner, Joakim

    2015-05-01

    Cervical screening programmes have reduced cervical cancer incidence and mortality but the level of success is highly variable between countries. Organisation of programmes is essential for equity and cost-effectiveness. However, there are differences in effectiveness, also among organised programmes. In order to identify the key organisational components that determine effectiveness, we performed a Europe-wide survey on the current status of organisation and organised quality assurance (QA) measures in cervical cancer prevention programmes, as well as organisation-associated costs. A comprehensive questionnaire was developed through systematic review of literature and existing guidelines. The survey was sent to programme organisers, Ministries of Health and experts in 34 European Union (EU) and European Free Trade Agreement (EFTA) countries. Detailed aspects of programme organisation, quality assurance, monitoring, evaluation and corresponding line-item costs were recorded. Documentation of programme guidelines, protocols and publications was requested. Twenty-nine of 34 countries responded. The results showed that organised efforts for QA, monitoring and evaluation were carried out to a differing extent and were not standardised, making it difficult to compare the cost-effectiveness of organisation and QA strategies. Most countries found it hard to estimate the costs associated with launching and operating the organised programme. To our knowledge, this is the first questionnaire to request detailed information on the actual organisation and QA of programmes. The results of this survey can be used as a basis for further development of standardised guidelines on organisation and QA of cervical cancer screening programmes in Europe. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Role of CDH13 promoter methylation in the carcinogenesis, progression, and prognosis of colorectal cancer

    PubMed Central

    Ye, Meng; Huang, Tao; Li, Jinyun; Zhou, Chongchang; Yang, Ping; Ni, Chao; Chen, Si

    2017-01-01

    Abstract Background: H-cadherin (CDH13) is commonly downregulated through promoter methylation in various cancers. However, the role of CDH13 promoter methylation status in patients with colorectal cancer (CRC) remains to be clarified. Methods: Eligible articles were identified from online electronic database based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. The pooled odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated and analyzed. Results: Eventually, a total of nine studies were included in this meta-analysis, including 488 CRC, 298 adjacent, 144 normal, 68 premalignant tissues. The results demonstrated that CDH13 promoter methylation was notably higher in CRC than in normal, adjacent, and premalignant tissues (cancer tissues vs normal tissues: OR = 16.94, P < 0.001; cancer tissues vs adjacent tissues: OR = 20.06, P < 0.001; cancer tissues vs premalignant tissues: OR = 2.23, P = 0.038). CDH13 promoter methylation had a significantly increased risk for poorly differentiated CRC (OR = 4.07, P = 0.001). CDH13 promoter methylation was not associated with sex status, tumor stage, and lymph node status (all P > 0.05). One study with 85 CRC patients reported that CDH13 promoter methylation was correlated with poor prognosis in overall survival (OS). Conclusions: CDH13 promoter methylation may play an important role in the initiation and progression of CRC, and may be correlated with OS of patients with CRC. Additional studies with large sample sizes are needed to further confirm our findings in the future. PMID:28121942

  12. [The prognosis and clinicopathological characteristics of 70 gastric cancer patients with elevated serum AFP].

    PubMed

    Wang, Y K; Shen, L; Zhang, X T

    2017-07-23

    Objective: This study aimed to review the clinicopathological characteristics and prognosis of advanced gastric cancer patients with elevated serum Alpha-fetoprotein (AFP). Methods: From August 2006 to May 2016, 70patients with advanced gastric cancer were enrolled retrospectively. All these patients had pathologically confirmed gastric adenocarcinoma, had a serum AFP level of more than 20 ng/ml, and received at least first-line treatment. The clinicopathological data and follow-up data were collected for analysis. Results: Liver metastasis was more common in patients with AFP≥1 000 ng/ml, compared with AFP<1 000 ng/ml patients (78.6% vs 57.1%, P=0.064). In patients whose AFP level decreased ≥50% after first-line chemotherapy, the disease control rate and overall survival were both better than those in patients with AFP decreased <50%(96.3% vs 56.7%, P=0.001; 17.2 m vs 8.8 m P=0.007). The overall survival of all these 70 patients ranged from 0.5-50.0 months. 31 patients received chemotherapy only, and 39 patients received combined therapy modality. The overall survival of these two groups were similar(11.0 m and 15.6 m, respectively, P=0.070). Conclusions: Serum AFP-elevated gastric cancer is a special subtype of gastric cancer. It's a heterogeneous cancer with different clinical outcomes. The extent of decrease of serum AFP level during follow-up may be a sensitive prognostic and predictive biomarker. Liver metastasis were more common in these patients, and combined treatment may improve survival.

  13. Type 2 diabetes mellitus and prognosis in early stage breast cancer women.

    PubMed

    Kaplan, Muhammet Ali; Pekkolay, Zafer; Kucukoner, Mehmet; Inal, Ali; Urakci, Zuhat; Ertugrul, Hamza; Akdogan, Recai; Firat, Ugur; Yildiz, Ismail; Isikdogan, Abdurrahman

    2012-09-01

    It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P < 0.001). The odds ratio of recurrence was significantly increased in those with HER2-neu overexpression and lymph node involvement and decreased with PR-positive tumors. Our results suggest that diabetes is an independent prognostic factor for breast cancer.

  14. Biomarkers Predict Prognosis of Esophageal Cancer Patients | Center for Cancer Research

    Cancer.gov

    New treatment strategies are needed to improve outcomes for patients with esophageal cancer. With five-year survival rates less than 25 percent, this is one of the deadliest forms of cancer. There are two main types of esophageal cancer—squamous cell carcinoma and adenocarcinoma. Esophageal adenocarcinoma is frequently preceded by Barrett’s esophagus, a chronic inflammatory condition caused by gastroesophageal reflux. It is known that communication between tumor cells and the immune system can alter the behavior of tumor cells, and chronic inflammation has been implicated in several types of human cancers, including cancer of the esophagus.

  15. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

    PubMed

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2015-01-01

    Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

  16. Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

    PubMed

    Kolarevic, Daniela; Tomasevic, Zorica; Dzodic, Radan; Kanjer, Ksenija; Vukosavljevic, Dragica Nikolic; Radulovic, Marko

    2015-10-01

    Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival.

  17. Downregulation of serum DKK-1 predicts poor prognosis in patients with papillary thyroid cancer.

    PubMed

    Zhao, Y P; Wang, W; Wang, X H; Xu, Y; Wang, Y; Dong, Z F; Zhang, J J

    2015-12-29

    The Wnt inhibitor dickkopf-1 (DKK-1) has been shown to be closely correlated with tumor initiation and progression in various types of cancers. However, the serum level of DKK-1 in patients with papillary thyroid cancer (PTC) and its potential clinical significance is poorly understood. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the level of serum DKK-1 in patients with PTC (N = 132) and healthy controls (N = 40). The association between serum DKK-1 level and clinicopathological parameters of PTC was examined and independent prognostic markers for PTC were identified. The mean serum DKK-1 level was significantly lower in patients with PTC than healthy controls (44.64 ± 15.13 and 85.51 ± 9.94 ng/mL, respectively; P < 0.01). Following treatment, the mean serum DKK-1 level in PTC patients significantly increased (67.03 ± 17.09 ng/mL; P < 0.01). Serum DKK-1 level was associated with various PTC clinical features including tumor size (P = 0.003), lymph node metastasis (P = 0.001), and tumor-node-metastasis stage (P = 0.004). Survival analysis revealed that PTC patients who had lower serum DKK-1 levels suffered both poorer overall survival (P = 0.036) and relapse-free survival (P = 0.015). Moreover, serum DKK-1 levels were an independent risk factor for predicting the prognosis of PTC (P = 0.031). In conclusion, low DKK-1 serum levels are associated with poor prognosis in PTC patients and DKK-1 could potentially be used as a biomarker leading to earlier diagnosis of PTC.

  18. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer

    PubMed Central

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2015-01-01

    Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy). PMID:26199650

  19. Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis

    PubMed Central

    Zhu, Xuejie; Hu, Xiaoli; Zheng, Lihong; Zhu, Xueqiong

    2017-01-01

    Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications. PMID:27911861

  20. A pathway to empowerment: evaluating a cancer education and support programme in New Zealand.

    PubMed

    Kane, P; Jasperse, M; Boland, P; Herst, P

    2014-09-01

    Support programmes often benefit cancer patients and their families. This study evaluates how the Living Well Cancer Education Programme (LWCEP), from the Cancer Society of New Zealand, meets the needs of its clients. A purposeful sample of 21 participants representing the normal range of demographic characteristics (age, gender, diagnosis and geographical location) for the programme, participated in semi-structured interviews. Demographic data were subjected to a frequency analysis. Main data were collected and analysed using a constructivist grounded theory approach regarding the experiences of the participants with being on the programme and recommendations for future development. Of the 21 participants, 14 were cancer patients (eight women and six men) and seven were support people (five women and two men). The LWCEP was described as a safe, supportive and stimulating environment, provided a powerful sense of belonging, empowered participants to gain perspective, enhance their confidence and communication skills and make increasingly informed choices. Consistent with a previous evaluation focussing on the facilitators of the LWCEP, there was a strong desire for better promotion of the programme to the wider community, establishment of a better referral pathway and the potential to offer two separate programmes depending on the stage of a patient's journey. © 2014 John Wiley & Sons Ltd.

  1. Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women

    PubMed Central

    Lee, Junsu; Choi, Jaesung; Chung, Seokang; Park, JooYong; Kim, Ji-Eun; Sung, Hyuna; Han, Wonshik; Lee, Jong Won; Park, Sue K.; Kim, Mi Kyung; Ahn, Sei-Hyun; Noh, Dong-Young; Yoo, Keun-Young; Kang, Daehee

    2017-01-01

    Purpose The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. Methods A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. Results The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. Conclusion The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women. PMID:28382092

  2. Incidence and Long-Term Prognosis of Cancer After Kidney Transplantation.

    PubMed

    Pendón-Ruiz de Mier, V; Navarro Cabello, M D; Martínez Vaquera, S; Lopez-Andreu, M; Aguera Morales, M L; Rodriguez-Benot, A; Aljama Garcia, P

    2015-11-01

    Malignancy is an important cause of mortality in renal transplants recipients. The incidence of cancer is increased by immunosuppressive treatment and longer kidney graft survival. The aim of this study was to evaluate the incidence, prognosis and survival of posttransplant malignancies: solid organ cancer (SOC), posttransplant lymphoproliferative disorder (PTLD), and nonmelanoma skin cancer (NMSC). We retrospectively studied the development of cancers among kidney transplants patients in our hospital from January 1979 to January 2015. We analyzed demographic and clinical characteristics, risk factors, and patient survival after tumor diagnosis. We included 1450 kidney transplants recipients with a mean follow-up was 10 years; among them, 194 developed malignancies. The mean age at presentation was 59 ± 10 years. The SOC, PTLD, and NMSC incidences were 6.2%, 1.2%, and 6%, respectively. The most common tumors were kidney (16.6%), colon (11%), bladder (10%), breast (10%), prostate (10%), and lung (8.8%). The median times to development of a SOC, PTLD, and NMSC were 6.86 (range, 3.7-12), 4.43 (range, 1.8-5.7), and 8.19 (range, 3.8-12.2) years, respectively. Risk factors associated with developing SOC and PTLD were patient age (odds ratio [OR], 1.03; P < .001) and time posttransplant (OR, 1.05; P = .02), whereas for NMSC were to be male (OR, 3.61; P < .001), to take calcineurin inhibitors (OR, 2.17; P = .034), patient age (OR, 1.05; P < .001) and time posttransplant (OR, 1.15; P < .01). The mean survival time from the diagnosis of SOC, PTLD, and NMSC were 2.09 (range, 0.1-5.3), 0.22 (range, 0.05-1.9), and 7.68 (range, 3.9-10.5) years, respectively (P < .001). SOC occurs more frequently than other malignancies among renal transplant patients. NMSC has better survival and prognosis. Older patients and prolonged graft function have a greater risk of developing malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers.

    PubMed Central

    Pujol, J. L.; Simony, J.; Jolimoy, G.; Jaffuel, D.; Demoly, P.; Quantin, X.; Marty-Ané, C.; Boher, J. M.; Charpentier, R.; Michel, F. B.

    1996-01-01

    index. Patients with a hypodiploid tumour had a shorter survival than patients with other DNA histogram patterns but, owing to the low frequency of hypodiploidy, this difference did not reach statistical significance. In Cox's proportional hazard model, an SCLC histology, an advanced tumour status, a positive nodal status and a hypodiploid tumour (hazard ratio: 2.070; 95% confidence interval 1.041-4.116) were significant determinants of survival. We conclude that hypodiploidy in lung cancer is a distinct DNA content abnormality as it contributes significantly to prognosis. Neither visually assessed nor computer-generated Ki-67 immunostaining measurements significantly determine prognosis. Images Figure 2 PMID:8826867

  4. Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer.

    PubMed

    Zhuo, Yang-Jia; Xi, Ming; Wan, Yue-Ping; Hua, Wei; Liu, Yuan-Ling; Wan, Song; Zhou, Yu-Lin; Luo, Hong-Wei; Wu, Shu-Lin; Zhong, Wei-De; Wu, Chin-Lee

    2015-04-01

    Centromere protein F (CENPF) is a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis. Previous studies have demonstrated that the upregulation of CENPF may be used as a proliferation marker of malignant cell growth in tumors. The overexpression of CENPF has also been reported to be associated with a poor prognosis in human cancers. However, the clinical significance of CENPF in prostate cancer (PCa) has not yet been fully elucidated. Thus, the aim of the present study was to determine the association of CENPF with tumor progression and prognosis in patients with PCa. The expression of CENPF at the protein level in human PCa and non-cancerous prostate tissues was detected by immunohistochemical analysis, which was further validated using a microarray-based dataset (NCBI GEO accession no: GSE21032) at the mRNA level. Subsequently, the association of CENPF expression with the clinicopathological characteristics of the patients with PCa was statistically analyzed. Immunohistochemistry and dataset analysis revealed that CENPF expression was significantly increased in the PCa tissues compared with the non-cancerous prostate tissues [immunoreactivity score (IRS): PCa, 177.98 ± 94.096 vs. benign, 121.30 ± 89.596, P < 0.001; mRNA expression in the dataset: PCa, 5.67 ± 0.47 vs. benign, 5.40 ± 0.11; P < 0.001]. Additionally, as revealed by the dataset, the upregulation of CENPF mRNA expression in the PCa tissues significantly correlated with a higher Gleason score (GS, P = 0.005), an advanced pathological stage (P = 0.008), the presence of metastasis (P < 0.001), a shorter overall survival (P=0.003) and prostate-specific antigen (PSA) failure (P < 0.001). Furthermore, both univariate and multivariate analyses revealed that the upregulation of CENPF was an independent predictor of poor biochemical recurrence (BCR)-free survival (P < 0.001 and P = 0.012, respectively). Our data suggest that the increased expression of CENPF

  5. Primary Recurrence in the Lung is Related to Favorable Prognosis in Patients with Pancreatic Cancer and Postoperative Recurrence.

    PubMed

    Zheng, Biao; Ohuchida, Kenoki; Yan, Zilong; Okumura, Takashi; Ohtsuka, Takao; Nakamura, Masafumi

    2017-06-20

    The pattern of recurrence affects the clinical outcome in tumor patients. However, the clinical significance of lung metastasis as the primary recurrence site after resection in patients with pancreatic cancer remains unclear. This study aimed to clarify the clinical significance of the primary recurrence site in patients with pancreatic cancer, in terms of prognosis and clinicopathological features. This retrospective cohort study included 220 patients with postoperative recurrence after pancreatectomy for pancreatic cancer and classified by primary site of recurrence. We focused on patients with lung metastasis as the primary recurrence and investigated its correlation with prognosis and clinicopathological factors. Twenty-four (11%) patients had lung metastasis as the primary recurrence. This recurrence pattern had the best prognosis among all recurrence patterns, including liver metastasis and local recurrence. Patients with lung metastasis as the primary recurrence had favorable overall survival and survival from the date of recurrence compared with patients with other primary recurrence sites in both univariate (P = 0.0008 and P = 0.0005) and multivariate analyses (P = 0.0051 and P = 0.0068). In terms of clinicopathological features of resected pancreatic tumors, lung metastasis as the primary recurrence was associated with lower tumor stage and histologic grade, and less vascular invasion and residual tumor volume than liver metastasis. Pancreatic cancer patients with lung metastasis as the primary recurrence after pancreatectomy have a better prognosis than those with other recurrence patterns.

  6. Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer

    PubMed Central

    Qing, Yi; Li, Qing; Ren, Tao; Xia, Wei; Peng, Yu; Liu, Gao-Lei; Luo, Hao; Yang, Yu-Xin; Dai, Xiao-Yan; Zhou, Shu-Feng; Wang, Dong

    2015-01-01

    Introduction Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer. Methods The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0. Results The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics. Conclusion The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis. PMID:25733810

  7. Are BRCA1- and BRCA2-associated breast cancers different? Prognosis of BRCA1-associated breast cancer.

    PubMed

    Robson, M

    2000-11-01

    To review the available literature regarding the outcome of breast cancer arising in the setting of a germline BRCA1 mutation. Reports of relevant studies obtained from a search of MEDLINE and studies referenced in those reports were reviewed. In addition, data from a previously published study of breast conservation therapy among women of Ashkenazi descent were reanalyzed to discern the effect of germline BRCA1 status. Although BRCA1-associated breast cancers have been associated repeatedly with poor prognostic features, studies that examine the impact of germline BRCA1 status on outcome have not consistently shown an adverse effect of BRCA1 mutations. In part, this may result from methodologic limitations of earlier trials. Recent studies that examine relatively unselected groups of Ashkenazi women have indicated a negative prognostic effect of specific BRCA1 mutations. It remains to be determined, however, whether BRCA1 status is an independent prognostic factor and whether the findings can be generalized to other mutations. BRCA1-associated breast cancers present with histopathologic features that seem to confer an adverse prognosis, at least in certain subgroups. However, it is not clear whether BRCA1 status has an independent effect on outcome. Until further data become available, treatment for BRCA1-associated breast cancer should be determined by the same factors that influence therapy of nonhereditary disease.

  8. Socioeconomic and ethnic inequities within organised colorectal cancer screening programmes worldwide.

    PubMed

    de Klerk, C M; Gupta, S; Dekker, E; Essink-Bot, M L

    2017-01-10

    Colorectal cancer (CRC) screening programmes can reduce CRC mortality. However, the implementation of a screening programme may create or exacerbate socioeconomic and ethnic health inequities if participation varies by subgroup. We determined which organised programmes characterise participation inequities by socioeconomic and ethnic subgroups, and assessed the variation in subgroup participation among programmes collecting group-specific data. Employing a literature review and survey among leaders of national or regional screening programmes, this study identified published and unpublished data on participation by socioeconomic status and ethnicity. We assessed programmes offering faecal occult blood tests (FOBT) for screening. Primary outcome was screening participation rate. Across 24 organised FOBT-screening programmes meeting the inclusion criteria, participation rates ranged from 21% to 73%. Most programmes (13/24, 54%) did not collect data on participation by socioeconomic status and ethnicity. Among the 11 programmes with data on participation by socioeconomic status, 90% (28/31 publications) reported lower participation among lower socioeconomic groups. Differences across socioeconomic gradients were moderate (66% vs 71%) to severe (35% vs 61%). Only six programmes reported participation results by ethnicity. Ethnic differences were moderate, though only limited data were available for evaluation. Across organised CRC screening programmes worldwide, variation in participation by socioeconomic status and ethnicity is often not assessed. However, when measured, marked disparities in participation by socioeconomic status have been observed. Limited data were available to assess inequities by ethnicity. To avoid exacerbating health inequities, screening programmes should systematically monitor participation by socioeconomic status and ethnicity, and investigate and address determinants of low participation. Published by the BMJ Publishing Group Limited. For

  9. Downregulation of the long noncoding RNA EGOT correlates with malignant status and poor prognosis in breast cancer.

    PubMed

    Xu, Shou-Ping; Zhang, Jin-Feng; Sui, Shi-Yao; Bai, Nan-Xia; Gao, Song; Zhang, Guang-Wen; Shi, Qing-Yu; You, Zi-Long; Zhan, Chao; Pang, Da

    2015-12-01

    Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P < 0.001), and low levels of EGOT expression were significantly correlated with larger tumor size (P = 0.022), more lymph node metastasis (P = 0.020), and higher Ki-67 expression (P = 0.017). Moreover, patients with low levels of EGOT expression showed significantly worse prognosis for overall survival (P = 0.040), and this result was further validated in a larger cohort from a public database. Multivariate analysis suggested that low levels of EGOT were a poor independent prognostic predictor for breast cancer patients (HR = 1.857, 95 % CI = 1.032-3.340, P = 0.039). In conclusion, EGOT may play an important role in breast cancer progression and prognosis and may serve as a new potential prognostic target in breast cancer patients.

  10. The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis

    PubMed Central

    Tang, Zhaoqing; Ma, Ji; Zhang, Wei; Gong, Changguo; He, Jing; Wang, Ying; Yu, Guohua; Yuan, Chonggang; Wang, Xuefei; Sun, Yihong; Ma, Jiyan; Liu, Fenglin; Zhao, Yulan

    2016-01-01

    Previous reports indicated that prion protein (PrP) is involved in gastric cancer (GC) development and progression, but its role in GC prognosis has been poorly characterized. A total of 480 GC patients were recruited in this retrospective study. PrP expression in cancerous and non-cancerous gastric tissues was detected by using the tissue microarray and immunohistochemical staining techniques. Our results showed that the PrP expression in GC was significantly less frequent than that in the non-cancerous gastric tissue (44.4% vs 66.4%, P < 0.001). Cox regression analysis revealed that PrP expression was associated with TNM stage, survival status and survival time. GC patients with higher TNM stages (stages II, III and IV) had significantly lower PrP expression levels in tumors than those with lower TNM stages (stages 0 and I). Kaplan-Meier survival curves revealed that negative PrP expression was associated with poor overall survival (log-rank test: P < 0.001). The mean survival time for patients with negative PrP expression was significant lower than those with positive PrP expression (43.0±28.5m vs. 53.9±31.1m, P<0.001). In multivariate Cox hazard regression, PrP expression was an independent prognostic factor for GC survival, with a HR (hazard ratio) of 0.687 (95%CI:0.520-0.907, P=0.008). Our results revealed that negative PrP expression could independently predict worse outcome in GC and thereby could be used to guide the clinical practice. PMID:27313789

  11. Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer?

    PubMed

    In Choi, Jeong; Chang, Ha Kyun; Lee, Dae Woo; Lee, Keun Ho; Park, Jong Sup; Lee, Hae Nam

    2015-11-01

    To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer. We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated. Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518). Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis

    PubMed Central

    Cai, Hong; Du, Chunyan; Liu, Xiaowen; Yu, Shengjia; Wang, Yanong

    2016-01-01

    Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein β-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer. PMID:27409174

  13. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    SciTech Connect

    Xu Zhiyuan; Marko, Nicholas F.; Chao, Sam T.; Angelov, Lilyana; Vogelbaum, Michael A.; Suh, John H.; Barnett, Gene H.; Weil, Robert J.

    2012-04-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  14. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer.

    PubMed

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-10-20

    There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

  15. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    PubMed Central

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-01-01

    Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. PMID:27775588

  16. Treatment and prognosis of breast cancer patients with brain metastases according to intrinsic subtype.

    PubMed

    Kuba, Sayaka; Ishida, Mayumi; Nakamura, Yoshiaki; Yamanouchi, Kosho; Minami, Shigeki; Taguchi, Kenichi; Eguchi, Susumu; Ohno, Shinji

    2014-11-01

    % confidence interval 1.5-5.8; P = 0.003, respectively). Our study showed that local brain treatments and prognosis differed by subtype in breast cancer patients with brain metastases. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer

    PubMed Central

    Erickson, Kirsten; Patterson, Ruth E.; Flatt, Shirley W.; Natarajan, Loki; Parker, Barbara A.; Heath, Dennis D.; Laughlin, Gail A.; Saquib, Nazmus; Rock, Cheryl L.; Pierce, John P.

    2011-01-01

    Purpose Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis. Methods Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival. Results Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk. Conclusion Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted. PMID:21115861

  18. Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

    PubMed Central

    Bria, E.; Pilotto, S.; Simbolo, M.; Fassan, M.; de Manzoni, G.; Carbognin, L.; Sperduti, I.; Brunelli, M.; Cataldo, I.; Tomezzoli, A.; Mafficini, A.; Turri, G.; Karachaliou, N.; Rosell, R.; Tortora, G.; Scarpa, A.

    2016-01-01

    In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC. PMID:26961069

  19. Evaluation of correlation between CT image features and ERCC1 protein expression in assessing lung cancer prognosis

    NASA Astrophysics Data System (ADS)

    Tan, Maxine; Emaminejad, Nastaran; Qian, Wei; Sun, Shenshen; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2014-03-01

    Stage I non-small-cell lung cancers (NSCLC) usually have favorable prognosis. However, high percentage of NSCLC patients have cancer relapse after surgery. Accurately predicting cancer prognosis is important to optimally treat and manage the patients to minimize the risk of cancer relapse. Studies have shown that an excision repair crosscomplementing 1 (ERCC1) gene was a potentially useful genetic biomarker to predict prognosis of NSCLC patients. Meanwhile, studies also found that chronic obstructive pulmonary disease (COPD) was highly associated with lung cancer prognosis. In this study, we investigated and evaluated the correlations between COPD image features and ERCC1 gene expression. A database involving 106 NSCLC patients was used. Each patient had a thoracic CT examination and ERCC1 genetic test. We applied a computer-aided detection scheme to segment and quantify COPD image features. A logistic regression method and a multilayer perceptron network were applied to analyze the correlation between the computed COPD image features and ERCC1 protein expression. A multilayer perceptron network (MPN) was also developed to test performance of using COPD-related image features to predict ERCC1 protein expression. A nine feature based logistic regression analysis showed the average COPD feature values in the low and high ERCC1 protein expression groups are significantly different (p < 0.01). Using a five-fold cross validation method, the MPN yielded an area under ROC curve (AUC = 0.669±0.053) in classifying between the low and high ERCC1 expression cases. The study indicates that CT phenotype features are associated with the genetic tests, which may provide supplementary information to help improve accuracy in assessing prognosis of NSCLC patients.

  20. FTO expression is associated with the occurrence of gastric cancer and prognosis.

    PubMed

    Xu, Dong; Shao, Weiwei; Jiang, Yasu; Wang, Xi; Liu, Ying; Liu, Xianchen

    2017-10-01

    Fat mass and obesity associated (FTO) is a protein-coding gene. FTO gene is an obesity related gene, also known as the obesity gene. It has been reported previously that FTO is associated with a variety of malignant cancers, such as breast, thyroid and endometrial cancer. The aim of the present study was investigate the FTO expression of human gastric cancer and to investigate its clinical value. FTO expression was determined by immunohistochemical analysis with tissue microarrays in GC tissues and corresponding adjacent non-tumor tissues. Moreover, the results in protein and mRNA level were confirmed by the real-time PCR and western blot analysis. The relationship between the FTO expression and the pathological characteristics of GC patients was also explored. In addition, by using MTT, clone formation and transwell assays, we studied the effects of FTO expression on biological function of GC cells in vitro. The Kaplan-Meier method and the log-rank test were used to compare the overall survival rate between the FTO high-expression group and the low-expression group. We affirmed repeatedly upregulation of FTO expression in both protein and mRNA levels in GC tissues compared to corresponding adjacent non-tumor tissues. Immunohistochemistry by tissue microarray of FTO expression was remarkably increased in GC tissues (72 of 128, 56.3%) compared with adjacent non-tumor tissues (24 of 62, 38.7%). FTO expression level was closely related to low differentiation (P<0.001), lymph node metastasis (P=0.029). The expression of FTO was positively correlated with TNM stage (P<0.001). the Kaplan-Meier analysis showed that high FTO expression was significantly associated with poor prognosis in GC patients. Downregulation of FTO expression significantly inhibited the proliferation, migration and invasion of GC cell lines. On the contrary, overexpression of FTO promoted the proliferation, migration and invasion of GC cell lines. This study indicates that FTO expression may have an

  1. [Meta-analysis of prognosis of ovarian preserving in young patients with early endometrial cancer].

    PubMed

    Wang, J; Li, X M

    2016-08-25

    To discuss the effect of preserving ovaries on the prognosis of young early endometrial cancer patients. Searched English and Chinese databases by computors, including Cochrane library, Embase, PubMed, Web of Science, China National Knowledge Internet (CNKI), data base of Wanfang, China Science and Technology Journal (CSTJ) , and also relevant journals and magazines by hand. Retrieval time from January 1996 to March 2016. In accordance with the inclusion criteria, two independent investigators screened the studies and extracted the relevant data respectively. Then evaluated the quality of included studies. Finally, conducted the meta-analysis with RevMan 5.3 software from cochrane collaboration network, in which heterogeneity test of enrolled studies firstly was completed and combined analysis with effect models according to the heterogeneity secondary. In the light of the result, effect of remaining ovaries on the prognosis (5-year recurrence rate and 5-year overall survival rate) of young early endometrial cancer patients was determined. Ten trials were included. All of them were cohort studies, a total of 5 299 patients, in which 916 patients' ovaries were remained. Quality assessment of all 10 studies were based on Newcastle-Ottawa Scale (NOS) scale. All of the studies enrolled were of high quality with a score of ≥7. After quality assessment,all studies illustrated the higher the quality. Meta-analysis showed that there was no statistically significant difference between who had ovarian preservation and without preservation in terms of 5-year overall survival rate [96.00% (863/899) vs 96.51% (3 736/3 871); RR=1.00, 95%CI: 0.99-1.02, P=0.792] and the 5-year recurrence rate [2.58% (7/271) vs 4.43% (51/1 150); RR=1.01, 95%CI: 0.46-2.22, P=0.986]. Ovarian preservation in young early stage patients of endometrial cancer could not effect the 5-year overall survival rateand the 5-year recurrence rate.

  2. Cancer stem cells: a systems biology view of their role in prognosis and therapy.

    PubMed

    Mertins, Susan D

    2014-04-01

    Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSCs). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of CSCs can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes.

  3. Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

    PubMed Central

    Mojarad, Ehsan Nazemalhosseini; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Taleghani, Mohammad Yaghoob; Azimzadeh, Pedram; Savabkar, Sanaz; Pourhoseingholi, Mohammad Amin; Jalaeikhoo, Hasan; Asadzadeh Aghdaei, Hamid; Kuppen, Peter J. K.; Zali, Mohammad Reza

    2016-01-01

    The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location. PMID:27429617

  4. Optically trapping tumor cells to assess differentiation and prognosis of cancers

    PubMed Central

    Pradhan, M.; Pathak, S.; Mathur, D.; Ladiwala, U.

    2016-01-01

    We report an optical trapping method that may enable assessment of the differentiation status of cancerous cells by determining the minimum time required for cell-cell adhesion to occur. A single, live cell is trapped and brought into close proximity of another; the minimum contact time required for cell-cell adhesion to occur is measured using transformed cells from neural tumor cell lines: the human neuroblastoma SK-N-SH and rat C6 glioma cells. Earlier work on live adult rat hippocampal neural progenitors/stem cells had shown that a contact minimum of ~5 s was required for cells to adhere to each other. We now find the average minimum time for adhesion of cells from both tumor cell lines to substantially increase to ~20-25 s, in some cases up to 45 s. Upon in vitro differentiation of these cells with all-trans retinoic acid the average minimum time reverts to ~5-7 s. This proof-of-concept study indicates that optical trapping may be a quick, sensitive, and specific method for determining differentiation status and, thereby, the prognosis of cancer cells. PMID:27231599

  5. Noncoding RNAs in the development, diagnosis, and prognosis of colorectal cancer.

    PubMed

    Weng, Mingjiao; Wu, Di; Yang, Chao; Peng, Haisheng; Wang, Guangyu; Wang, Tianzhen; Li, Xiaobo

    2017-03-01

    More than 90% of the human genome is actively transcribed, but less than 2% of the total genome encodes protein-coding RNA, and thus, noncoding RNA (ncRNA) is a major component of the human transcriptome. Recently, ncRNA was demonstrated to play important roles in multiple biological processes by directly or indirectly interfering with gene expression, and the dysregulation of ncRNA is associated with a variety of diseases, including cancer. In this review, we summarize the function and mechanism of miRNA, long intergenic ncRNA, and some other types of ncRNAs, such as small nucleolar RNA, circular ncRNA, pseudogene RNA, and even protein-coding mRNA, in the progression of colorectal cancer (CRC). We also presented their clinical application in the diagnosis and prognosis of CRC. The summary of the current state of ncRNA in CRC will contribute to our understanding of the complex processes of CRC initiation and development and will help in the discovery of novel biomarkers and therapeutic targets for CRC diagnosis and treatment.

  6. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer

    PubMed Central

    Cavanna, Luigi; Dall'Agata, Monia; Tassinari, Davide; Leo, Silvana; Bernardini, Ilaria; Gelsomino, Fabio; Tamberi, Stefano; Brandes, Alba A.; Tenti, Elena; Vespignani, Roberto; Frassineti, Giovanni L.; Amadori, Dino; De Giorgi, Ugo

    2016-01-01

    Background To investigate the role of pre-treatment inflammatory indexes (II) as predictors of prognosis and treatment efficacy in patients with metastatic colorectal cancer mCRC randomized onto the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) with or without bevacizumab (Bev). Results In the overall population, PFS and OS were higher in patients with low SII (p = .015 and .002, respectively), low NLR (p = .0001 and <.0001, respectively) and low PLR (p = .004 and .008, respectively). Patients with low NLR in the CT plus Bev arm had a higher PFS than those treated with CT alone (HR = 0.69, p = .021). Patients and Methods Two hundred and eighty-nine patients were considered for this study, 141 receiving CT plus Bev and 148 receiving CT alone. The pre-treatment systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were evaluated to identify a potential correlation with progression-free (PFS) and overall survival (OS) in both the overall population and the 2 treatment arms. Conclusion Our results indicate that II, in particular NLR, are good prognostic and predictive markers for mCRC patients who are candidates for CT plus Bev. PMID:27120807

  7. Underweight status predicts a poor prognosis in elderly patients with colorectal cancer

    PubMed Central

    Kaneko, Manabu; Sasaki, Shin; Ozaki, Kosuke; Ishimaru, Kazuhiro; Terai, Emi; Nakayama, Hiroshi; Watanabe, Toshiyuki

    2016-01-01

    The aim of the present study was to evaluate the effect of underweight status on the survival of elderly patients undergoing surgery for colorectal cancer (CRC). A total of 113 patients aged ≥75 years who underwent curative surgery for CRC were included. In addition to standard perioperative variables, body mass index (BMI) was assessed. The patients were categorized as underweight (BMI<18.5 kg/m2) or non-underweight (BMI≥18.5 kg/m2). The 3-year overall survival (OS) and cancer-specific survival (CSS) were analyzed. Of the 113 patients, 24 (21%) were underweight. The two groups were well-balanced regarding all factors evaluated. In the multivariate analysis, underweight status was an independent indicator of lower 3-year OS [hazard ratio (HR)=2.65; 95% confidence interval (CI): 1.08–6.50; P=0.033] and CSS (HR=3.51, 95% CI: 1.16–10.60; P=0.025) rates. Compared with the non-underweight group, the underweight group had significantly worse 3-year OS (66.7 vs. 86.5%, respectively; P=0.017) and CSS (74.1 vs. 90.9%, respectively; P=0.025) rates. Therefore, underweight status was a significant risk factor for poor survival in elderly CRC patients. The development of effective nutritional interventions may improve the prognosis of such patients. PMID:27602223

  8. MMP16 is a marker of poor prognosis in gastric cancer promoting proliferation and invasion

    PubMed Central

    Cao, Li; Chen, Chaowu; Zhu, Haihang; Gu, Xuewen; Deng, Denghao; Tian, Xiuchun; Liu, Jun; Xiao, Qin

    2016-01-01

    Matrix metalloproteinases (MMPs) are closely associated with tumor proliferation, invasion and metastasis. In this study, we determined the MMPs expression and their clinical significances in gastric cancer (GC). We first extensive studied MMPs expression in GC in The Cancer Genome Atlas (TCGA) RNA sequence database and found MMP16 was candidate biomarker in GC. Then we validated clinical significance of MMP16 mRNA expression in 167 GC by RT-PCR. Survival analysis showed that high expression of MMP16 indicated poor overall and disease free survival (P<0.001). The proliferation and invasion potential of GC cells were determined by CCK8, colony formation and Transwell assays. Silencing of MMP16 expression significantly decreased the invasion and proliferation capacity of GC cells (P<0.05). In conclusion, MMP16 was highly expressed and correlated with poor prognosis in GC patients by promoting proliferation and invasion of GC cells. MMP16 could be a novel molecular target and prognostic marker for GC. PMID:27340864

  9. Identification of CEACAM5 as a Biomarker for Prewarning and Prognosis in Gastric Cancer.

    PubMed

    Zhou, Jinfeng; Fan, Xing; Chen, Ning; Zhou, Fenli; Dong, Jiaqiang; Nie, Yongzhan; Fan, Daiming

    2015-12-01

    MGd1, a monoclonal antibody raised against gastric cancer cells, possesses a high degree of specificity for gastric cancer (GC). Here we identified that the antigen of MGd1 is CEACAM5, and used MGd1 to investigate the expression of CEACAM5 in non-GC and GC tissues (N=643), as a biomarker for prewarning and prognosis. The expression of CEACAM5 was detected by immunohistochemistry in numerous tissues; its clinicopathological correlation was statistically analyzed. CEACAM5 expression was increased progressively from normal gastric mucosa to chronic atrophic gastritis, intestinal metaplasia, dysplasia and finally to GC (p<0.05). In gastric precancerous lesions (intestinal metaplasia and dysplasia), CEACAM5-positive patients had a higher risk of developing GC as compared with CEACAM5-negative patients (OR = 12.68, p<0.001). Besides, CEACAM5 was found positively correlated with invasion depth of gastric adenocarcinoma (p<0.001). In survival analysis, CEACAM5 was demonstrated to be an independent prognostic predictor for patients with GC of clinical stage IIIA/IV (p=0.033). Our results demonstrate that CEACAM5 is a promising biomarker for GC prewarning and prognostic evaluation.

  10. Stroma-associated master regulators of molecular subtypes predict patient prognosis in ovarian cancer.

    PubMed

    Zhang, Shengzhe; Jing, Ying; Zhang, Meiying; Zhang, Zhenfeng; Ma, Pengfei; Peng, Huixin; Shi, Kaixuan; Gao, Wei-Qiang; Zhuang, Guanglei

    2015-11-04

    High-grade serous ovarian carcinoma (HGS-OvCa) has the lowest survival rate among all gynecologic cancers and is hallmarked by a high degree of heterogeneity. The Cancer Genome Atlas network has described a gene expression-based molecular classification of HGS-OvCa into Differentiated, Mesenchymal, Immunoreactive and Proliferative subtypes. However, the biological underpinnings and regulatory mechanisms underlying the distinct molecular subtypes are largely unknown. Here we showed that tumor-infiltrating stromal cells significantly contributed to the assignments of Mesenchymal and Immunoreactive clusters. Using reverse engineering and an unbiased interrogation of subtype regulatory networks, we identified the transcriptional modules containing master regulators that drive gene expression of Mesenchymal and Immunoreactive HGS-OvCa. Mesenchymal master regulators were associated with poor prognosis, while Immunoreactive master regulators positively correlated with overall survival. Meta-analysis of 749 HGS-OvCa expression profiles confirmed that master regulators as a prognostic signature were able to predict patient outcome. Our data unraveled master regulatory programs of HGS-OvCa subtypes with prognostic and potentially therapeutic relevance, and suggested that the unique transcriptional and clinical characteristics of ovarian Mesenchymal and Immunoreactive subtypes could be, at least partially, ascribed to tumor microenvironment.

  11. Epigenetic modulation associated with carcinogenesis and prognosis of human gastric cancer.

    PubMed

    Sonohara, Fuminori; Inokawa, Yoshikuni; Hayashi, Masamichi; Kodera, Yasuhiro; Nomoto, Shuji

    2017-05-01

    Gastric cancer (GC) is a leading cause of cancer-related death, particularly in Asia. Epidemiological and other clinical studies have identified an association between a number of risk factors, including Helicobacter pylori, and GC. A number of studies have also examined genetic changes associated with the development and progression of GC. When considering the clinical significance of the expression of a specific gene, its epigenetic modulation should be considered. Epigenetic modulation appears to be a primary driver of changes in gastric tissue that promotes carcinogenesis and progression of GC and other neoplasms. The role of epigenetic modulation in GC carcinogenesis and progression has been widely studied in recent years. In the present review, recent results of epigenetic modulation associated with GC and their effects on clinical outcome are examined, with particular respect to DNA methylation, histone modulation and non-coding RNA. A number of studies indicate that epigenetic changes in the expression of specific genes critically affect their clinical significance and further study may reveal epigenetic changes as the basis for targeted molecular therapy or novel biomarkers that predict GC prognosis or extension of this often fatal disease.

  12. Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

    ClinicalTrials.gov

    2017-08-19

    Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  13. Preoperative serum markers for individual patient prognosis in stage I-III colon cancer.

    PubMed

    Giessen-Jung, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Schulz, Christoph; Heinemann, Volker; Di Gioia, Dorit; Stieber, Petra

    2015-09-01

    Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve

  14. Expression of Tim-3 in gastric cancer tissue and its relationship with prognosis.

    PubMed

    Cheng, Gui; Li, Min; Wu, Jun; Ji, Mei; Fang, Cheng; Shi, Hongbing; Zhu, Danxia; Chen, Lujun; Zhao, Jiemin; Shi, Liangrong; Xu, Bin; Zheng, Xiao; Wu, Changping; Jiang, Jingting

    2015-01-01

    As a negative regulatory molecule, T-cell immunoglobulin-and mucin domain-3 (Tim-3) plays a crucial role in the tumor immunological tolerance. In the present study, we aimed to determine the Tim-3 expression in gastric cancer tissue and its relationship with clinicopathological parameters and prognosis. The Tim-3 expression was assessed in 52 gastric cancer specimens and 15 gastritis tissues by flow cytometry, and gastritis tissues served as the control. As a result, we found that the Tim-3 expressions on CD4(+)T cells and CD8(+)T cells in gastric cancer tissue was significantly higher than those in gastritis tissue (P=0.022, P=0.047, respectively). The median expression level of Tim-3 on CD4(+)T cells were significantly correlated with clinicopathological parameters, such as tumor size, lymph node metastasis, the depth of tumor invasion and TNM staging (P=0.042, P=0.026, P=0.001, P=0.003, respectively), while it was not correlated with sex, age and histological subtype (all P>0.05). In CD8(+)T cells, the Tim-3 expression was relevant to tumor invasion and TNM staging (P=0.035, P=0.017, respectively), while it was irrelevant to other clinicopathological parameters (all P>0.05). Additionally, Kaplan-Meier survival curves showed that the median overall survival time of patients with lower Tim-3 expression was greater than that of patients with higher Tim-3 expression in CD4(+)T cells and CD8(+)T cells (χ(2)=18.036, P<0.001 and χ(2)=18.036, P<0.001, respectively). Moreover, the multivariate analysis revealed that the Tim-3 expression and TNM stage were independent prognostic factors for gastric cancer patients (P=0.029, P=0.043 and P=0.003, respectively). These results suggest that Tim-3 played an important role in the development and progression of gastric cancer, and it could be used as an independent prognostic factor for gastric cancer patients.

  15. The Role of GOLPH3L in the Prognosis and NACT response in Cervical Cancer

    PubMed Central

    Feng, Yanling; He, Fan; Yan, Shumei; Huang, He; Huang, Qidan; Deng, Ting; Wu, Huini; Gao, Bei; Liu, Jihong

    2017-01-01

    -antibody array suggested GOLPH3L plays a role in mediating cell cycle arrest. Conclusions: This study provides a potential biomarker for predicting prognosis and NACT response in patients with cervical squamous cell carcinoma. The functional role of GOLPH3L in cervical cancer merits further investigation. PMID:28261346

  16. [Association of serum albumin level with clinicopathologic features and prognosis in colon cancer].

    PubMed

    Jiang, Zhiqiang; Li, Yalan; Han, Guangsen; Zhang, Jian; Li, Zhi; Wang, Daohai; Liu, Yingjun

    2016-01-01

    To evaluate the clinical significance of preoperative serum albumin level and its association with survival in colon cancer patients. Clinicopathological data of 621 consecutive patients with colon cancer admitted in Henan Cancer Hospital between January 2000 and December 2008 were retrospectively analyzed. These patients were divided into hypoalbuminemic and normal groups according to the definition of hypoalbuminemia (serum albumin < 35 g/L). Clinicopathological features were compared between two groups. The association of preoperative serum albumin level and the prognosis was analyzed by Kaplan-Meier and Log-rank test. Multivariate Cox model was used to evaluate the survival. Sixty-seven(10.8%) patients were defined as preoperative hypoalbuminemia and were mostly found in those with right hemicolon cancer. Preoperative serum albumin level was associated with depth of tumor (χ(2)=35.609, P=0.000), lymph node metastasis (χ(2)=8.110, P=0.004), distant metastasis (χ(2)=9.064, P=0.003), advanced TNM T staging (χ(2)=23.070, P=0.000), and not associated with age, gender, tumor gross type, histological type, and degree of tumor differentiation (all P>0.05). 5-year survival rate of hypoalbuminemia group and normal group was 55.2% and 66.1% respectively (P=0.032). Univariate analysis revealed age (P=0.000), tumor gross type (P=0.014), degree of tumor differentiation (P=0.014), depth of tumor (P=0.000), lymph node metastasis (P=0.001), distant metastasis (P=0.000), advanced TNM T staging (P=0.000), operative method (P=0.000) and preoperative serum albumin level (P=0.032) were associated with survival. Cox multivariate analysis revealed the albumin level was the independent prognostic factor of the 5-year overall survival (HR:0.694, 95% CI: 0.492-0.980, P=0.038). The patients with higher albumin level had better survival outcome. Preoperative serum albumin level is an independent prognostic factor for colon cancer. Colon cancer patients with hypoalbuminemia have worse

  17. T-cadherin is associated with prognosis in triple-negative breast cancer.

    PubMed

    Kong, De-Di; Wang, Mei-Hong; Yang, Jie; Li, Liang; Wang, Wei; Wang, Shi-Bing; Zhou, Yan-Zhen

    2017-09-01

    The purpose of the present study was to assess the prognostic impact of T-cadherin expression in patients with triple-negative breast cancer (TNBC). On the basis of the results of immunohistochemical analysis, 106 patients with operable TNBC were divided into two groups, the T-cadherin-positive group and T-cadherin-negative group. Fisher's exact and χ(2) tests were employed to analyze clinical data, which included the association between T-cadherin expression and clinicopathological features and prognosis. The log-rank test was used to examine the impact of T-cadherin expression on the 5-year disease-free survival (DFS) and the 5-year overall survival (OS) of these patients. Kaplan-Meier and Cox regression analyses were introduced to analyze DFS and OS. Compared with the T-cadherin-positive group (58.3, 52.8 and 47.2, respectively; P=0.018, P=0.017, and P=0.047), tumor size >2 cm, grade II and III (Elston-Ellis modification of Bloom-Richardson grading system), and positive lymph node status were significantly more common in the T-cadherin-negative group compared with the T-cadherin-positive group (80.0 vs. 58.3%, 75.7 vs. 52.8% and 67.1 vs. 47.2%, respectively) (P=0.018, P=0.017, and P=0.047). Compared with the T-cadherin-positive group, 5-year DFS and OS levels were significantly lower in the T-cadherin-negative group (Z=6.233, P=0.013; Z=5.366, P=0.021). Multivariate analysis revealed that negative T-cadherin expression was an independent prognostic factor for DFS (P=0.009) and OS (P=0.048). The results of the present study indicated that negative T-cadherin expression indicated a worse prognosis for patients with TNBC.

  18. Expression of THOP1 and Its Relationship to Prognosis in Non-Small Cell Lung Cancer

    PubMed Central

    Qi, Lei; Li, Shu-hai; Si, Li-bo; Lu, Ming; Tian, Hui

    2014-01-01

    Background The study was designed to detect the expression level of thimet oligopeptidase (THOP1) protein in non-small cell lung cancer (NSCLC) and investigate its correlation with clinicopathologic features and prognosis. Methods Immunohistochemical staining was used to determine the expression of THOP1 protein in 120 NSCLC specimens and 53 distant normal lung tissues. Quantitative real-time PCR and western blotting were employed to measure the expression of THOP1 in 16 pairs of primary NSCLC and corresponding normal tissues. Results Analysis of immunohistochemical staining suggested low THOP1 expression was found in 71 (59.2%) of the 120 NSCLC specimens and significantly correlated with positive lymph node metastasis (P = 0.048). However, low THOP1 expression was found in 22 (41.5%) of the 53 normal lung tissues. Chi-square test suggested that the expression of THOP1 was significantly higher in the normal lung tissues than that in the NSCLC specimens (P = 0.032). Real-Time PCR and western blotting showed that NSCLC specimens had decreased THOP1 mRNA and protein expression compared to corresponding normal tissues. Univariate analysis demonstrated that low THOP1 expression significantly predicted decreased 5-year disease-free survival (P = 0.038) and overall survival (P = 0.017). In addition, positive lymph node metastasis (P = 0.025) and advanced TNM stage (P = 0.009) significantly predicted decreased 5-year overall survival. However, multivariate Cox regression analysis showed that only low THOP1 expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival (P = 0.046) and overall survival (P = 0.021). Conclusions THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC. PMID:25180910

  19. Breast cancer in young women and prognosis: How important are proliferation markers?

    PubMed

    Fredholm, Hanna; Magnusson, Kristina; Lindström, Linda S; Tobin, Nicholas P; Lindman, Henrik; Bergh, Jonas; Holmberg, Lars; Pontén, Fredrik; Frisell, Jan; Fredriksson, Irma

    2017-08-24

    Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis. Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins. Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]). The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Impact of platelet to lymphocyte ratio and metabolic syndrome on the prognosis of colorectal cancer patients.

    PubMed

    You, Jie; Zhang, Huxiang; Shen, Yanyan; Chen, Chuanzhi; Liu, Wenyue; Zheng, Minghua; Van Poucke, Sven; Guo, Guilong; Huang, Zonghai

    2017-01-01

    The aim of this study was to evaluate the prognostic value of both platelet to lymphocyte ratio (PLR) and metabolic syndrome (MetS) in colorectal cancer (CRC) patients. We retrospectively enrolled 1,163 CRC patients. Preoperative values of PLR were stratified into three groups according to cut-off values of 120 and 220. The Kaplan-Meier analysis was used to calculate cumulative survival rate related to PLR and MetS. Cox proportional hazard regression models were used to analyze potential risk factors and the prognosis associated with PLR and MetS in CRC patients. PLR was significantly higher in the MetS(+) group as compared to MetS(-) group (P=0.039). An elevated PLR was significantly associated with mortality (P=0.014), but not the existence of MetS (P=0.235). In multivariate regression analysis, PLR was an independent risk factor for overall survival (OS) (P=0.046). For the subgroup with a PLR >220, MetS was an independent predictor for both OS and disease-free survival (P=0.039 and P=0.047, respectively) by multivariate analysis adjusting for confounding covariates. In addition, the presence of MetS was associated with a 2-fold increased risk of mortality and tumor recurrences (hazard ratio [HR] =2.0 and HR =1.9, P<0.05, respectively). Preoperative PLR was associated with MetS in CRC patients. Testing for the combined presence of PLR and MetS could potentially improve the predictive accuracy of CRC prognosis.

  1. Cancer stem cell markers predict a poor prognosis in renal cell carcinoma: a meta-analysis

    PubMed Central

    Cheng, Bo; Yang, Guosheng; Jiang, Rui; Cheng, Yong; Yang, Haifan; Pei, Lijun; Qiu, Xiaofu

    2016-01-01

    Background Relevant markers of CSCs may serve as prognostic biomarkers of RCC. However, their actual prognostic significance remains inconclusive. Thus, a meta-analysis was performed to reevaluate the association of CSCs-relevant markers (CXCR4, CD133, CD44, CD105) expression with RCC prognosis more precisely. Methods PubMed and Embase were searched to look for eligible studies. The pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were used to reassess the association of CSCs markers expression and RCC prognosis of overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). Results There were 25 relevant articles, encompassing 2673 RCC patients, eligible for meta-analysis. Overall pooled analysis suggested that high CSCs markers expression predicted poor OS (HR, 2.10, 95% CI: 1.73–2.55) and DFS (HR, 3.77, 95% CI: 2.30–6.19). High CXCR4 expression predicted worse OS (HR, 2.57, 95% CI: 1.95–3.40), CSS (HR,1.97, 95% CI: 1.50–2.59), and DFS (HR, 5.82, 95% CI: 3.01–11.25). CD44 over-expression correlated with a poor OS(HR,1.58, 95% CI: 1.14–2.18), CSS (HR, 2.58, 95% CI: 1.27–5.23), and DFS (HR, 4.49, 95% CI: 2.12–9.53) in RCC patients. CD133 was an independent favorable prognostic factor for CSS (HR, 0.4, 95% CI: 0.29–0.54). Conclusions The presence of CSCs markers correlates with poor RCC outcome. CSCs may be potentially utilized as prognostic markers to stratify RCC patients, probably representing also a novel potential therapeutic target. PMID:27588469

  2. Predictive gene lists for breast cancer prognosis: A topographic visualisation study

    PubMed Central

    Sivaraksa, Mingmanas; Lowe, David

    2008-01-01

    Background The controversy surrounding the non-uniqueness of predictive gene lists (PGL) of small selected subsets of genes from very large potential candidates as available in DNA microarray experiments is now widely acknowledged [1]. Many of these studies have focused on constructing discriminative semi-parametric models and as such are also subject to the issue of random correlations of sparse model selection in high dimensional spaces. In this work we outline a different approach based around an unsupervised patient-specific nonlinear topographic projection in predictive gene lists. Methods We construct nonlinear topographic projection maps based on inter-patient gene-list relative dissimilarities. The Neuroscale, the Stochastic Neighbor Embedding(SNE) and the Locally Linear Embedding(LLE) techniques have been used to construct two-dimensional projective visualisation plots of 70 dimensional PGLs per patient, classifiers are also constructed to identify the prognosis indicator of each patient using the resulting projections from those visualisation techniques and investigate whether a-posteriori two prognosis groups are separable on the evidence of the gene lists. A literature-proposed predictive gene list for breast cancer is benchmarked against a separate gene list using the above methods. Generalisation ability is investigated by using the mapping capability of Neuroscale to visualise the follow-up study, but based on the projections derived from the original dataset. Results The results indicate that small subsets of patient-specific PGLs have insufficient prognostic dissimilarity to permit a distinction between two prognosis patients. Uncertainty and diversity across multiple gene expressions prevents unambiguous or even confident patient grouping. Comparative projections across different PGLs provide similar results. Conclusion The random correlation effect to an arbitrary outcome induced by small subset selection from very high dimensional interrelated

  3. Pregnancy-associated breast cancer in women from Shanghai: risk and prognosis.

    PubMed

    Strasser-Weippl, Kathrin; Ramchandani, Ritesh; Fan, Lei; Li, Junjie; Hurlbert, Marc; Finkelstein, Dianne; Shao, Zhi-Ming; Goss, Paul E

    2015-01-01

    Breast cancer (BC) has been associated with pregnancy if diagnosed within 5-10 years after delivery (pregnancy-associated BC, PABC). PABC carries a poor prognosis compared to sporadic BC in Western populations. Data are limited regarding PABC in Asian populations, where longer periods of breastfeeding, higher birth rates and a lower median age of BC at diagnosis have been noted, all of which are known to influence prognosis. We used two datasets of women treated for early BC in Shanghai 1990-2012 (n = 10,161 and n = 7,411). For the analysis of BC risk after pregnancy we compared the distribution of pregnancy in our dataset to that in Shanghai using age-specific fertility rates. For disease-free survival (DFS) evaluation, we restricted our data to women ≤45 years. Women <30 years had a significantly elevated BC risk within 5 years of completing a pregnancy compared to women who had not been pregnant in the previous 5 years. In women aged 20-24 the relative risk (RR) was 3.33 (P = 0.012), and for women aged 25-29 the RR was 1.76 (P = 0.0074). For women >30, the RR was decreased. Patients with PABC had a higher risk of recurrence or death (hazard ratio (HR) for DFS 1.72, P = 0.019) compared to women with non-PABC by univariable analysis. Age was eliminated from the multivariable model by backward selection, resulting in tumor stage (3 versus 1, HR 3.08, P < .001) and recent pregnancy (HR 1.62, P < 0.05) as significant independent prognosticators. Having had a full-term pregnancy in the previous 5 years was associated with a 62 % increased risk of recurrence. We show that recent full-term pregnancy significantly elevates BC risk in women <30 in Shanghai, and that women diagnosed with PABC have a particularly adverse prognosis. Health care providers and women in Asian populations should be made aware of these results.

  4. Disclosure and understanding of cancer diagnosis and prognosis for people with intellectual disabilities: findings from an ethnographic study.

    PubMed

    Tuffrey-Wijne, Irene; Bernal, Jane; Hollins, Sheila

    2010-07-01

    Growing numbers of people with intellectual disabilities are diagnosed with a life-limiting illness such as cancer. Little is known about disclosure of diagnosis and prognosis to this group. The study aim was to explore how much people with intellectual disabilities who have cancer understand about their diagnosis and prognosis, and to explore how much they are told about their cancer. 13 people with intellectual disabilities and cancer took part in a 3-year ethnographic study. Data collection consisted mostly of participant observation. Participants were visited regularly for a median of 7 months. Eleven participants were told that they had cancer, but most were not helped to understand the implications of this diagnosis or their prognosis. Decisions around disclosure, as well as the task of truth-telling, rested mostly with relatives and paid carers. Those with severe/profound intellectual disabilities were most likely to be protected from the truth. Understanding was affected by cognitive ability, life experience and truth-telling. Lack of understanding affected the ability to take decisions about treatment and care. Existing models for breaking bad news are inadequate for people with intellectual disabilities. The findings suggest that more open communication is needed, but further studies are needed to establish best practice in this area.

  5. Generation of 2,000 breast cancer metabolic landscapes reveals a poor prognosis group with active serotonin production

    PubMed Central

    Leoncikas, Vytautas; Wu, Huihai; Ward, Lara T.; Kierzek, Andrzej M.; Plant, Nick J.

    2016-01-01

    A major roadblock in the effective treatment of cancers is their heterogeneity, whereby multiple molecular landscapes are classified as a single disease. To explore the contribution of cellular metabolism to cancer heterogeneity, we analyse the Metabric dataset, a landmark genomic and transcriptomic study of 2,000 individual breast tumours, in the context of the human genome-scale metabolic network. We create personalized metabolic landscapes for each tumour by exploring sets of active reactions that satisfy constraints derived from human biochemistry and maximize congruency with the Metabric transcriptome data. Classification of the personalized landscapes derived from 997 tumour samples within the Metabric discovery dataset reveals a novel poor prognosis cluster, reproducible in the 995-sample validation dataset. We experimentally follow mechanistic hypotheses resulting from the computational study and establish that active serotonin production is a major metabolic feature of the poor prognosis group. These data support the reconsideration of concomitant serotonin-specific uptake inhibitors treatment during breast cancer chemotherapy. PMID:26813959

  6. Invitation coverage and participation in Italian cervical, breast and colorectal cancer screening programmes.

    PubMed

    Giorgi Rossi, Paolo; Carrozzi, Giuliano; Federici, Antonio; Mancuso, Pamela; Sampaolo, Letizia; Zappa, Marco

    2017-01-01

    Objectives In Italy, regional governments organize cervical, breast and colorectal cancer screening programmes, but there are difficulties in regularly inviting all the target populations and participation remains low. We analysed the determinants associated with invitation coverage of and participation in these programmes. Methods We used data on screening programmes from annual Ministry of Health surveys, 1999-2012 for cervical, 1999-2011 for breast and 2005-2011 for colorectal cancer. For recent years, we linked these data to the results of the national routine survey on preventive behaviours to evaluate the effect of spontaneous screening at Province level. Invitation and participation relative risk were calculated using Generalized Linear Models. Results There is a strong decreasing trend in invitation coverage and participation in screening programmes from North to South Italy. In metropolitan areas, both invitation coverage (rate ratio 0.35-0.96) and participation (rate ratio 0.63-0.88) are lower. An inverse association exists between spontaneous screening and both screening invitation coverage (1-3% decrease in invitation coverage per 1% spontaneous coverage increase) and participation (2% decrease in participation per 1% spontaneous coverage increase) for the three programmes. High recall rate has a negative effect on invitation coverage in the next round for breast cancer (1% decrease in invitation per 1% recall increase). Conclusions Organizational and cultural changes are needed to better implement cancer screening in southern Italy.

  7. High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer.

    PubMed

    Hamano, R; Miyata, H; Yamasaki, M; Sugimura, K; Tanaka, K; Kurokawa, Y; Nakajima, K; Takiguchi, S; Fujiwara, Y; Mori, M; Doki, Y

    2012-04-10

    Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated. Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line. Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells. High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.

  8. Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer

    PubMed Central

    Yamanoi, Koji; Matsumura, Noriomi; Murphy, Susan K.; Baba, Tsukasa; Abiko, Kaoru; Hamanishi, Junzo; Yamaguchi, Ken; Koshiyama, Masafumi; Konishi, Ikuo; Mandai, Masaki

    2016-01-01

    Anoikis resistance is a hallmark of cancer, and relates to malignant phenotypes, including chemoresistance, cancer stem like phenotypes and dissemination. The aim of this study was to identify key factors contributing to anoikis resistance in ovarian cancer using a functional genomics screen. A library of 81 000 shRNAs targeting 15 000 genes was transduced into OVCA420 cells, followed by incubation in soft agar and colony selection. We found shRNAs directed to ABHD2, ELAC2 and CYB5R3 caused reproducible anoikis resistance. These three genes are deleted in many serous ovarian cancers according to The Cancer Genome Atlas data. Suppression of ABHD2 in OVCA420 cells increased phosphorylated p38 and ERK, platinum resistance, and side population cells (p<0.01, respectively). Conversely, overexpression of ABHD2 decreased resistance to anoikis (p<0.05) and the amount of phosphorylated p38 and ERK in OVCA420 and SKOV3 cells. In clinical serous ovarian cancer specimens, low expression of ABHD2 was associated with platinum resistance and poor prognosis (p<0.05, respectively). In conclusion, we found three novel genes relevant to anoikis resistance in ovarian cancer using a functional genomics screen. Suppression of ABHD2 may promote a malignant phenotype and poor prognosis for women with serous ovarian cancer. PMID:27323405

  9. Prostate specific G protein coupled receptor is associated with prostate cancer prognosis and affects cancer cell proliferation and invasion.

    PubMed

    Cao, Wenqing; Li, Faqian; Yao, Jorge; Yu, Jiangzhou

    2015-11-18

    There is limited information about the clinical and biological significance of prostate specific G protein coupled receptor (PSGR) in prostate cancer (PCa) initiation and progression. Here, we evaluated the expression of PSGR protein, studied its diagnostic and prognostic value in PCa, and also explored its role in cancer cell growth and invasion. The expression of PSGR in paired adjacent normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and PCa were determined by immunohistochemistry on tissue microarrays constructed from 150 radical prostatectomy specimens. The effects of PSGR on PCa cell growth and invasion were investigated using human PCa cell lines. Membranous and cytoplasmic PSGR staining was observed at luminal epithelial cells of prostate. PSGR protein expression was significantly higher in PIN compared to normal prostate. Interestingly, the expression of PSGR decreased as PIN progressed to PCa. Low PSGR expression in PCa was associated with high Gleason score, and poor overall survival. Activated PSGR increased cancer cell invasive ability, but retarded cell growth. PSGR did not affect mTOR activity, but suppressed P70 S6 kinase activity. PSGR may participate in PCa progression through affecting cell proliferation and invasion. High expression of PSGR in PIN may implicate its role in early neoplastic transformation of PCa. Low expression of PSGR in PCa may serve as a potential indicator for poor prognosis.

  10. FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer.

    PubMed

    Habashy, Hany Onsy; Rakha, Emad A; Aleskandarany, Mohammed; Ahmed, Mohamed Ah; Green, Andrew R; Ellis, Ian O; Powe, Desmond G

    2011-08-01

    Oestrogen receptor (ER)-positive breast cancer (BC) constitutes a heterogeneous group of tumours with regard to outcome and response to therapy. Accurate stratification of ER-positive BC according to risk of relapse and response to therapy will be achieved through an improved understanding of ER and ER-related biological pathways. Recent studies have identified Forkhead box O3a (FOXO3a) transcription factor as an intracellular mediator of ERα expression and as an important downstream target of the Akt/PI3K pathway indicating a biological and potential clinical role for FOXO3a in ER-positive BC. In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer. FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1 and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (P < 0.001) and longer distant metastasis free interval (P = 0.001), independently of the well-established breast cancer prognostic factors. In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localisation in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.

  11. Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

    PubMed

    Fonseca, Mariana Bertoldi; Gomes, Francisco Hugo Rodrigues; Valera, Elvis Terci; Pileggi, Gecilmara Salviato; Gonfiantini, Paula Braga; Gonfiantini, Marcela Braga; Ferriani, Virgínia Paes Leme; Carvalho, Luciana Martins de

    2016-12-16

    To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase (LDH) was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition. Copyright © 2016. Published by Elsevier Editora Ltda.

  12. Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

    PubMed

    Fonseca, Mariana Bertoldi; Gomes, Francisco Hugo Rodrigues; Valera, Elvis Terci; Pileggi, Gecilmara Salviato; Gonfiantini, Paula Braga; Gonfiantini, Marcela Braga; Ferriani, Virgínia Paes Leme; Carvalho, Luciana Martins de

    To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

  13. Metallothionein isoform 3 overexpression is associated with breast cancers having a poor prognosis.

    PubMed

    Sens, M A; Somji, S; Garrett, S H; Beall, C L; Sens, D A

    2001-07-01

    The third isoform (MT-3) of the metallothionein gene family is unique in that it has a limited tissue distribution, is not induced by metals, has a neuronal growth inhibitory activity, and sequesters zinc more effectively under zinc-depleted conditions. The goal of the present study was to determine whether MT-3 was absent in normal breast tissue, was overexpressed in breast cancers, and if MT-3 overexpression would be associated with disease outcome. A combination of immunohistochemistry and reverse-transcription polymerase chain reaction was used to demonstrate that the normal breast had no detectable expression of MT-3 mRNA or protein. Using immunohistochemistry, it was shown that MT-3 was overexpressed in 25 of 34 cases of breast cancer. In all cases of positive staining, MT-3 was diffusely localized to the cytoplasm. The tumors from these 34 cases were divided as to outcome based on known 5-year survival, with 20 patients being disease free at 5 years (good outcome) and the other 14 having recurring disease within 5 years (bad outcome). When analyzed for MT-3 staining, it was shown that there was a trend for increased MT-3 immunoreactivity in the group having bad outcomes. However, when the tumor subgrouping was further defined on the basis of carcinoma in situ (CIS), there was a marked significant difference in MT-3 staining between patients with good and bad outcomes. Limited to DCIS, MT-3 staining was significantly increased in patients with bad outcomes compared to those with good outcomes. Thus, these studies demonstrate that MT-3 is overexpressed in selected breast cancers and that overexpression is associated with tumors having a poor prognosis.

  14. Patient Generated Subjective Global Assessment as a prognosis tool in women with gynecologic cancer.

    PubMed

    Rodrigues, Camila Santos; Lacerda, Marina Seraphim; Chaves, Gabriela Villaça

    2015-01-01

    The aim of this study was to assess the nutritional status (NS) of women hospitalized for gynecologic tumors and relate it to such outcomes as hospital length of stay and 1-y mortality. We assessed 146 women diagnosed with gynecologic tumors who were admitted to a referral oncologic hospital in November 2012. Data collected included medical history, duration and reason for admission, and cases of death within 1 y. NS was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The receiver operating characteristic curve was used to define the best cutoff point for discriminating individuals who did or did not die. We used proportional hazards regression to assess associations between malnutrition and 1-y mortality. According to the PG-SGA, 62.4% of the women were classified as being at nutritional risk or having moderate or severe malnutrition. Sorting patients by stage of cancer, there was no statistical difference in NS classification according to the different cancer sites. The median hospital stay, in days, was statistically lower in patients classified as well nourished. Individuals with a score above the cutoff point of 10 were 30.7 times more likely (95% confidence interval, 11.8-79.4) to die. There was a 52.1% rate of mortality within 1 y. Patients classed as having some degree of malnutrition had a significantly lower median survival rate. A diagnosis of cervical cancer and severe malnourishment increases the likelihood of death. Our findings suggest that the PG-SGA can be considered not just as an indicator of nutritional risk, but also as a major predictor of prognosis and mortality in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Clinicopathological features and prognosis of triple negative breast cancer in Kuwait: A comparative/perspective analysis☆

    PubMed Central

    Fayaz, Mohammed S.; El-Sherify, Mustafa S.; El-Basmy, Amany; Zlouf, Sadeq A.; Nazmy, Nashwa; George, Thomas; Samir, Susan; Attia, Gerges; Eissa, Heba

    2013-01-01

    Aim The aim of this study was to determine the incidence of TNBC in Kuwait, to analyze the clinicopathologic features and prognosis of this type of breast cancer, and compare it with reports from other regions of the world. Background Triple negative breast cancer (TNBC) is defined as a subtype that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). There is a growing evidence of the heterogeneity of such entity on the molecular level that may cause discrete outcomes. Methods We analyzed the clinicopathologic features of 363 TNBC cases which were diagnosed in Kuwait from July 1999 to June 2009. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan–Meier method. Comparison was done with reports from USA, Europe, Middle and Far East. Results Among 2986 patients diagnosed with breast cancer in Kuwait, 363 patients (12.2%) were TNBC. The median age was 48 years, 57.2% had lymph nodes (LN) metastasis, 56.9% were of grade III tumor and 41.9% had stage II disease. 81% developed recurrences and 75% of deaths occurred by 2.5 years after treatment. There is marked variation of clinicopathologic features according to country of patients’ cohort. Conclusion The incidence of TNBC in our study is similar to other studies. TNBC patients showed an early major recurrence surge peaking at approximately year 2.5. Regional variation of clinicopathologic features indicates a need for molecular studies to define underlying molecular features and its impact on survival. PMID:24936335

  16. Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

    PubMed Central

    Chang, Jeremy T-H.; Wang, Fan; Chapin, William; Huang, R. Stephanie

    2016-01-01

    Breast cancer is the second-most common cancer and second-leading cause of cancer mortality in American women. The dysregulation of microRNAs (miRNAs) plays a key role in almost all cancers, including breast cancer. We comprehensively analyzed miRNA expression, global gene expression, and patient survival from the Cancer Genomes Atlas (TCGA) to identify clinically relevant miRNAs and their potential gene targets in breast tumors. In our analysis, we found that increased expression of 12 mature miRNAs—hsa-miR-320a, hsa-miR-361-5p, hsa-miR-103a-3p, hsa-miR-21-5p, hsa-miR-374b-5p, hsa-miR-140-3p, hsa-miR-25-3p, hsa-miR-651-5p, hsa-miR-200c-3p, hsa-miR-30a-5p, hsa-miR-30c-5p, and hsa-let-7i-5p —each predicted improved breast cancer survival. Of the 12 miRNAs, miR-320a, miR-361-5p, miR-21-5p, miR-103a-3p were selected for further analysis. By correlating global gene expression with miRNA expression and then employing miRNA target prediction analysis, we suggest that the four miRNAs may exert protective phenotypes by targeting breast oncogenes that contribute to patient survival. We propose that miR-320a targets the survival-associated genes RAD51, RRP1B, and TDG; miR-361-5p targets ARCN1; and miR-21-5p targets MSH2, RMND5A, STAG2, and UBE2D3. The results of our stringent bioinformatics approach for identifying clinically relevant miRNAs and their targets indicate that miR-320a, miR-361-5p, and miR-21-5p may contribute to breast cancer survival. PMID:27959953

  17. Discrepancies between public perceptions and epidemiological facts regarding cancer prognosis and incidence in Japan: an Internet survey.

    PubMed

    Takahashi, Miyako; Kai, Ichiro; Muto, Takashi

    2012-10-01

    This study investigates discrepancies between Japanese public perceptions and epidemiological facts regarding cancer prognosis and lifetime incidence, as well as factors that correlate with public perceptions. We conducted a cross-sectional Internet survey with 2369 Japanese survey registrants without a history of cancer. Survey registrants were selected so that distributions of gender, age and place of residence (prefecture) reflected 2010 national census data as much as possible. The questionnaire included questions about their perceptions of 5-year survival rates for cancer in general and 19 site-specific cancers, as well as their perceptions of cumulative lifetime cancer incidence rate among Japanese men and women. The distribution of respondent answers regarding the 5-year survival rate for cancer in general and 19 site-specific cancers varied widely from epidemiological data. Multiple regression analyses revealed that in some cancers, respondents who were of older age, who were female and who had a family/friend with a cancer history were significantly more likely to provide higher estimates regarding the 5-year survival rates. Respondents who correctly estimated cumulative lifetime cancer incidence rates among Japanese men and women were 8.5 and 33.1%, respectively. Respondents who were young, who had a higher educational background and who had a family/friend with a cancer history were significantly more likely to provide higher estimates of cumulative lifetime cancer incidence rates. Our study revealed wide discrepancies between Japanese public perceptions and epidemiological facts for cancer prognosis and incidence. Accordingly, more efforts should be made to bridge the gap between incorrect perceptions and epidemiological facts.

  18. Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer.

    PubMed

    Robinson, Penelope J; Bell, Robin J; Davis, Susan R

    2014-11-01

    Whether moderate to severe obesity (body mass index (BMI)≥30 to <40kg/m(2)) contributes to breast cancer recurrence and mortality remains uncertain. 1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis. Of the 1155 included women, mean age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, p<0.001), OAET (HR=0.26, 95%CI 0.14-0.46, p<0.001), mastectomy (HR=3.28, 95%CI 1.98-5.44, p<0.001) and radiotherapy (HR=2.12, 95%CI 1.24-3.63, p=0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event. Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Loss of constitutive ABCB1 expression in breast cancer associated with worse prognosis.

    PubMed

    Delou, João Marcos de Azevedo; Vignal, Giselle Maria; Índio-do-Brasil, Vanessa; Accioly, Maria Theresa de Souza; da Silva, Taiana Sousa Lopes; Piranda, Diogo Nascimento; Sobral-Leite, Marcelo; de Carvalho, Marcelo Alex; Capella, Márcia Alves Marques; Vianna-Jorge, Rosane

    2017-01-01

    constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.

  20. [Association of peripheral nerve invasion with clinicopathological factors and prognosis of colorectal cancer].

    PubMed

    Han, Dong; Wei, Ying; Wang, Xidi; Wang, Geng; Chen, Yinggang

    2017-01-25

    To investigate the association of peripheral nerve invasion (PNI) with clinicopathological factors and prognosis of colorectal cancer. Clinicopathological data and Surgical specimens of 372 colorectal cancer patients who underwent radical resection from January 2011 to June 2012 in The Second Affiliated Hospital of Harbin Medical University were collected. Histopathological evaluation of tissue samples was conducted with hematoxylin and eosin-stained sections. PNI was considered positive when cancer cells were observed inside the nerve sheath, or when at least 33% of the nerve periphery was surrounded by cancer cells. The relationship between PNI and clinicopathological factors of colorectal cancer was analyzed by χ(2) test or Fisher's exact test. Three-year overall survivals of PNI positive and negative patients were determined using the Kaplan-Meier method. Detection results were compared using log-rank test. Of 372 colorectal cancer patients, 133 (35.8%) were PNI positive. Among the PNI positive patients, 63 cases were male and 70 cases female; 76 cases were more than 60 years old and 57 cases less than 60 years old; tumors of 6 cases located in the ileocecal colon, of 33 cases in the ascending colon, of 7 cases in the transverse colon, of 8 cases in the descending colon, of 22 cases in the sigmoid colon, and of 57 cases in the rectum; tumor diameter was greater than 4 cm in 83 cases, and less than 4 cm in 50 cases; tumors of 48 cases were moderately or highly differentiated, and of 85 cases poorly-differentiation; tumor invasion depth in 2 cases, T2 in 7 cases, T3 in 93 cases, T4 in 31 cases; lymphatic metastasis was N0 phase in 56 cases, N1 in 41 cases, and N2 in 36 cases; tumors were stage I( in 2 cases, stage II( in 40 cases, of stage III( in 75 cases and stage IIII( in 16 cases. The positive rate of PNI was significantly associated with tumor location (χ(2)=11.20, P=0.048), tumor size (χ(2)=21.80, P=0.000), differentiation (χ(2)=60.90, P=0.000), depth

  1. The Effect of Diabetes Mellitus on Lung Cancer Prognosis: A PRISMA-compliant Meta-analysis of Cohort Studies.

    PubMed

    Zhu, Linhai; Cao, Hongxin; Zhang, Tiehong; Shen, Hongchang; Dong, Wei; Wang, Liguang; Du, Jiajun

    2016-04-01

    Previous studies suggested that diabetes mellitus (DM) was associated with risk and mortality of cancer, but studies investigating the correlation between DM and lung cancer prognosis remain controversial. Herein, a meta-analysis was performed to derive a more precise estimate of the prognostic role of DM in lung cancer.Medline and Embase were searched for eligible articles from inception to October 25, 2015. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) was calculated to evaluate the correlation between DM and lung cancer prognosis. Subgroup meta-analysis was performed based on the histology and the treatment methods.A total of 20 cohort studies from 12 articles were included in the meta-analysis. Also, 16 studies investigated the overall survival (OS) and 4 studies investigated the progression-free survival (PFS). DM was significantly associated with the inferior OS of lung cancer with the pooled HR 1.28 (95% CI: 1.10-1.49, P = 0.001). The association was prominent in the nonsmall cell lung cancer (NSCLC) subgroup (HR 1.35, 95%CI: 1.14-1.60, P = 0.002), whereas the association was not significant in the small cell lung cancer (SCLC) subgroup (HR 1.33, 95% CI: 0.87-2.03, P = 0.18). When NSCLC patients were further stratified by treatment methods, DM had more influence on the surgically treated subgroup than the nonsurgically treated subgroup. There was no obvious evidence for publication bias by Begg's and Egger's test.The results of this meta-analysis exhibit an association of DM with inferior prognosis amongst lung cancer patients, especially the surgically treated NSCLC patients. Given the small number of studies included in this meta-analysis, the present conclusion should be consolidated with more high-quality prospective cohort studies or randomized controlled trials.

  2. Gender differences in the correlation between prognosis and postoperative weight loss in patients with non-small cell lung cancer.

    PubMed

    Kawai, Hideki; Saito, Yoshitaro; Suzuki, Yohei

    2017-04-21

    : The aim of this study was to investigate gender differences in the relationship between preoperative body mass index (BMI), postoperative body weight change and prognosis in patients with non-small cell lung cancer (NSCLC). : Two hundred and sixty-three patients with NSCLC were enrolled in this study. Preoperative BMI was categorized based on WHO definition as follows: underweight (BMI <18.5): 21 patients (8.0%), normal (18.5 ≦ BMI <25): 179 patients (68%), overweight and obese (BMI ≧25): 63 patients (24%). Several factors such as age, sex, cancer stage, body weight change and BMI were recorded and correlated to the postoperative overall survival (OS). : For male patients, those in the low-BMI group had the worst prognosis ( P  < 0.05) whereas female patients with low BMI did not. Male patients with low BMI had statistically significant poorer prognosis compared to corresponding female patients ( P  < 0.05). Male patients with more than 5% body weight loss within 1 year after operation when compared to preoperative body weight had poorer prognosis than those with less than 5% body weight loss ( P  < 0.001). Furthermore, these male patients had statistically significant worse prognosis than the corresponding female patients ( P  < 0.05). In multivariable analysis, gender, more than 5% of body weight loss compared to preoperative body weight, and pathological stage were independent prognostic factors in NSCLC. : This study illustrates significant gender differences in the relationship between prognosis and BMI or body weight change in patients with postoperative NSCLC.

  3. CXC chemokine receptor 1 predicts postoperative prognosis and chemotherapeutic benefits for TNM II and III resectable gastric cancer patients

    PubMed Central

    Lin, Chao; Li, Ruochen; Wu, Songyang; Li, He; He, Hongyong; Zhang, Weijuan; Xu, Jiejie

    2017-01-01

    Backround Abnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer. Methods 330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining. The relation between CXCR1 expression and clinicopathological features and postoperative prognosis was respectively inspected. Results In both discovery and validation data sets, CXCR1 high expression indicated poorer overall survival (OS) in TNM II and III patients. Furthermore, multivariate analysis identified CXCR1 expression and TNM stage as two independent prognostic factors for OS. Incorporating CXCR1 expression into current TNM staging system could generate a novel clinical predictive model for gastric cancer, showing better prognostic accuracy with respect to patients’ OS. More importantly, TNM II patients with higher CXCR1 expression were shown to significantly benefit from postoperative 5-fluorouracil (5-FU) based adjuvant chemotherapy (ACT). Conclusion CXCR1 in gastric cancer was identified as an independent adverse prognostic factor. Combining CXCR1 expression with current TNM staging system could lead to better risk stratification and more accurate prognosis for gastric cancer patients. High expression of CXCR1 identified a subgroup of TNM stage II gastric cancer patients who appeared to benefit from 5-FU based ACT. PMID:27780937

  4. CXC chemokine receptor 1 predicts postoperative prognosis and chemotherapeutic benefits for TNM II and III resectable gastric cancer patients.

    PubMed

    Cao, Yifan; Liu, Hao; Zhang, Heng; Lin, Chao; Li, Ruochen; Wu, Songyang; Li, He; He, Hongyong; Zhang, Weijuan; Xu, Jiejie

    2017-03-21

    Backround: Abnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer. 330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining. The relation between CXCR1 expression and clinicopathological features and postoperative prognosis was respectively inspected. In both discovery and validation data sets, CXCR1 high expression indicated poorer overall survival (OS) in TNM II and III patients. Furthermore, multivariate analysis identified CXCR1 expression and TNM stage as two independent prognostic factors for OS. Incorporating CXCR1 expression into current TNM staging system could generate a novel clinical predictive model for gastric cancer, showing better prognostic accuracy with respect to patients' OS. More importantly, TNM II patients with higher CXCR1 expression were shown to significantly benefit from postoperative 5-fluorouracil (5-FU) based adjuvant chemotherapy (ACT). CXCR1 in gastric cancer was identified as an independent adverse prognostic factor. Combining CXCR1 expression with current TNM staging system could lead to better risk stratification and more accurate prognosis for gastric cancer patients. High expression of CXCR1 identified a subgroup of TNM stage II gastric cancer patients who appeared to benefit from 5-FU based ACT.

  5. Elevated expression of tumor miR-222 in pancreatic cancer is associated with Ki67 and poor prognosis.

    PubMed

    Lee, ChongLek; He, Hang; Jiang, Yongjian; Di, Yang; Yang, Feng; Li, Ji; Jin, Chen; Fu, Deliang

    2013-12-01

    Pancreatic cancer is known for its bad prognosis. Micro-RNAs mis-expressions are associated with various human cancers and offer new candidate targets for diagnostic and therapeutic strategies. Micro-RNA-222 has been shown to play a crucial role in cancer cell proliferation in recent studies. However, its correlations with the clinicopathological characters of pancreatic cancer still remain unclear. Through a prospective study of 60 pairs of pancreatic cancer tissues, adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between the expression of micro-RNA-222 and clinico-pathological characters was performed using the two-sample Student's t test. The survival correlations were analyzed by the Kaplan-Meier method and the Cox's proportional hazards model. Results showed that the expression levels of micro-RNA-222 were significantly elevated in the pancreatic cancer tissue compared with that in adjacent normal tissue. In addition, the overexpression of the tissue micro-RNA-222 strongly related to the expression level of Ki67. Finally, Cox's proportional hazards model analysis confirmed that micro-RNA-222 high expression level was an independent predictor of poor prognosis. This study provides the first evidence of a potential link between Ki67 and micro-RNA-222, which are both relevant to cell proliferation. Our data suggest the potential of micro-RNA-222 as a prognostic biomarker for the pancreatic cancer.

  6. National industry's interest in colorectal cancer screening programmes.

    PubMed Central

    Hart, A R; Barone, T L; Wicks, A C; Mayberry, J F

    1994-01-01

    The interest of the largest 200 British industries in developing and financing colorectal screening services for employees was determined. A standard questionnaire asked if the company would advertise screening supply names of employees to local hospitals and finance faecal occult blood testing. The reasons for rejection were noted. Eighty-six companies returned the questionnaire (43% response rate) of which 78 firms (39% of the total mailed) were prepared to advertise screening programmes at the workplace. A quarter of the companies were prepared to both advertise and release employee details. Companies willing to participate employed significantly more people (mean of 17,000 employees) than those rejecting screening (mean of 6100 employees, Mann-Whitney U test = 7, P < 0.05). Fifty-nine industries would consider financing screening, although only five made a definite decision to do so. All companies rejecting (36/36) were concerned about releasing employee information to hospitals. If screening does reduce mortality and community programmes are developed industry could and is prepared to advertise such programmes. If a partnership between hospitals and industry is developed, concerns about employee confidentiality needs to be addressed. PMID:7837182

  7. A CD44-specific peptide, RP-1, exhibits capacities of assisting diagnosis and predicting prognosis of gastric cancer.

    PubMed

    Li, Weiming; Jia, Huan; Wang, Jichang; Guan, Hao; Li, Yan; Zhang, Dan; Tang, Yanan; Wang, Thomas D; Lu, Shaoying

    2017-05-02

    Early diagnosis and evaluation of prognosis are both crucial for preventing poor prognosis of patients with gastric cancer (GC), a leading cause of cancer-related deaths worldwide. Cluster of differentiation 44 (CD44), an indicator of cancer stem cells, can be specifically targeted by molecular probes and detected in tissues of GC in a large quantity. In current study we found that RP-1, a specific peptide binding to CD44 protein, exhibited the potentials of specific binding to CD44 high-expressing cancer cells both in vitro and in vivo, and the capacity of predicting prognosis of human GC in a microarray assay. Results showed that RP-1 was characterized by high affinity, sensitivity and specificity, and low toxicity, suggesting RP-1 could be an ideal bio-probe for accessory diagnosis of GC. Further immunohistochemical studies and statistical analysis of tissue microarray of human GC demonstrated similar sensitivity and specificity of RP-1 with the monoclonal anti-CD44 antibody in the diagnosis of GC, and even proved that positive RP-1 could be an independent risk factor. Therefore, this study suggests RP-1 has the potentials of binding to CD44 protein expressed on the membrane of GC cells, and demonstrates the feasibility and reliability of its further application in molecular diagnosis and prognostic prediction of GC.

  8. A CD44-specific peptide, RP-1, exhibits capacities of assisting diagnosis and predicting prognosis of gastric cancer

    PubMed Central

    Li, Weiming; Jia, Huan; Wang, Jichang; Guan, Hao; Li, Yan; Zhang, Dan; Tang, Yanan; Wang, Thomas D.; Lu, Shaoying

    2017-01-01

    Early diagnosis and evaluation of prognosis are both crucial for preventing poor prognosis of patients with gastric cancer (GC), a leading cause of cancer-related deaths worldwide. Cluster of differentiation 44 (CD44), an indicator of cancer stem cells, can be specifically targeted by molecular probes and detected in tissues of GC in a large quantity. In current study we found that RP-1, a specific peptide binding to CD44 protein, exhibited the potentials of specific binding to CD44 high-expressing cancer cells both in vitro and in vivo, and the capacity of predicting prognosis of human GC in a microarray assay. Results showed that RP-1 was characterized by high affinity, sensitivity and specificity, and low toxicity, suggesting RP-1 could be an ideal bio-probe for accessory diagnosis of GC. Further immunohistochemical studies and statistical analysis of tissue microarray of human GC demonstrated similar sensitivity and specificity of RP-1 with the monoclonal anti-CD44 antibody in the diagnosis of GC, and even proved that positive RP-1 could be an independent risk factor. Therefore, this study suggests RP-1 has the potentials of binding to CD44 protein expressed on the membrane of GC cells, and demonstrates the feasibility and reliability of its further application in molecular diagnosis and prognostic prediction of GC. PMID:28415792

  9. Multimodal Cancer Care in Poor Prognosis Cancers: Resection Drives Long-Term Outcomes

    PubMed Central

    Healy, Mark A.; Yin, Huiying; Wong, Sandra L.

    2016-01-01

    Background and Objectives Hospitals with high complex oncologic surgical volume have improved short-term outcomes. However, for long-term outcomes, the influence of other therapies must be considered. We compared effects of resection with other therapies on long-term outcomes across U.S. hospitals. Methods We examined claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset for patients with esophageal (EC) and pancreatic (PC) cancers between 2005–2009, with follow-up through 2011, performing multivariable Cox proportional hazards analyses. We stratified hospitals by volume and compared rates of treatments in the context of survival. Results We studied 905 EC and 3,293 PC patients at 138 and 375 hospitals, respectively. For EC, resection rates were significantly higher (32.9% vs. 9.5%, P<0.001) in the highest versus lowest volume hospitals. Adjusted survival was also statistically significantly better (48.5% vs. 43.1%, P<0.001). For PC, resection rates were also statistically significantly higher (30.1% vs. 12.0%, P<0.001) with higher adjusted survival (21.5% vs. 19.9%, P = 0.01). We did not find variation in rates of other cancer treatments across hospitals. Conclusions A significant association exists between long-term survival and rates of cancer-directed surgery across hospitals, without variation in rates of other therapies. Access to resection appears to be key to reducing variation in long-term survival. PMID:26953166

  10. A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients.

    PubMed

    Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

    2017-07-01

    An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.

  11. A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients

    PubMed Central

    Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

    2017-01-01

    An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa. PMID:28693168

  12. Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.

    PubMed

    Sabatier, Renaud; Lavit, Elise; Moretta, Jessica; Lambaudie, Eric; Noguchi, Tetsuro; Eisinger, François; Cherau, Elisabeth; Provansal, Magali; Livon, Doriane; Rabayrol, Laetitia; Popovici, Cornel; Charaffe-Jauffret, Emmanuelle; Sobol, Hagay; Viens, Patrice

    2016-10-01

    Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

  13. Between prevention and therapy: Gio Batta Gori and the National Cancer Institute's Diet, Nutrition and Cancer Programme, 1974-1978.

    PubMed

    Cantor, David

    2012-10-01

    This paper explores the origins of the Diet, Nutrition and Cancer Programme (DNCP) of the National Cancer Institute (NCI) and its fate under its first director, Gio Batta Gori. The DNCP is used to explore the emergence of federal support for research on diet, nutrition and cancer following the 1971 Cancer Act, the complex relations between cancer prevention and therapeutics in the NCI during the 1970s, the broader politics around diet, nutrition and cancer during that decade, and their relations to Senator George McGovern's select committee on Nutrition and Human Needs. It also provides a window onto the debates and struggles over whether NCI research should be funded by contracts or grants, the nature of the patronage system within the federal cancer research agency, how a director, Gio Gori, lost patronage within that system and how a tightening of the budget for cancer research in the mid-to-late 1970s affected the DNCP.

  14. Discussions of life expectancy moderate relationships between prognosis and anxiety or depression in men with advanced cancer.

    PubMed

    Cripe, Larry D; Rawl, Susan M; Schmidt, Karen K; Tong, Yan; Monahan, Patrick O; Rand, Kevin L

    2012-01-01

    Oncologists avoid prognostic discussions due to concerns about increasing patients' anxiety or depression. We sought to determine if perceived prognosis or extent of prognostic discussions predicted anxiety or depression and whether prognostic discussions moderated the relationship between prognosis and anxiety or depression. Men with advanced cancer and their oncologists estimated the likelihood of survival at 6 months and reported extent of prognostic discussions. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Men who died within 6 months reported higher scores on depression but not anxiety. Men who estimated a lower (10%-75%) likelihood of surviving at least 6 months were more depressed and anxious than men who estimated a higher (>90%) likelihood of survival. A similar relationship was seen with oncologists' prognostications. Men who reported having had full prognostic discussions with their oncologist had less depression compared with men who reported having had brief or no discussions. Men for whom the oncologists reported a full discussion had greater anxiety. The relationships between patient-perceived prognosis and depression or anxiety were moderated by extent of prognostic discussions as reported by the patient or oncologist, respectively. Full prognostic discussions are associated with less depression among men who perceive a poor prognosis. Anxiety is increased in men if the oncologists report a full discussion. Oncologists should engage in prognostic discussions but assess for increased anxiety to facilitate coping with advanced cancer.

  15. Coexistence of MSI with KRAS mutation is associated with worse prognosis in colorectal cancer

    PubMed Central

    Hu, Jing; Yan, Wen-Yue; Xie, Li; Cheng, Lei; Yang, Mi; Li, Li; Shi, Jiong; Liu, Bao-Rui; Qian, Xiao-Ping

    2016-01-01

    Abstract Kristen rat sarcoma viral oncogene homolog (KRAS) and microsatellite instability (MSI) are prognostic markers of colorectal cancer (CRC). However, the clinical value is still not fully understood, when giving the consideration to both the molecular makers. Five hundred fifty-one patients with CRC were retrospectively assessed by determining their clinicopathological features. KRAS mutations were detected by polymerase chain reaction. MSI, a defect in the mismatch repair (MMR) system, was detected by immunohistochemistry. The prognostic value of KRAS in combination with MSI was studied. Among 551 CRC patients, mutations in KRAS codon 12 and KRAS codon 13 were detected in 34.5% and 10.5% of patients, respectively. Four hundred one tumors were randomly selected to detect for MMR proteins expression. In this analysis, 30 (7.5%) tumors that had at least 1 MMR protein loss were defined as MMR protein-deficient (MMR-D), and the remaining tumors were classed as MMR protein-intact (MMR-I). According to KRAS mutation and MSI status, CRC was classified into 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group4 had the best prognosis. In conclusion, combination status of KRAS and MSI status may be used as a prognostic biomarker for CRC patient, if validated by larger studies. PMID:27977612

  16. Overexpression of long noncoding RNA HOTTIP promotes tumor invasion and predicts poor prognosis in gastric cancer

    PubMed Central

    Ye, Heng; Liu, Kun; Qian, Keqing

    2016-01-01

    Purpose Long noncoding RNAs have been proved to play important roles in the tumorigenesis and development of human gastric cancer (GC). Our study aims to investigate the expression and function of Homeobox A transcript at the distal tip (HOTTIP) in GC. Methods HOTTIP expression was detected in GC tissues and cell lines by using quantitative reverse transcription polymerase chain reaction. Association between HOTTIP levels and clinicopathological factors and patient prognosis was also analyzed. MTT, flow cytometry, and transwell invasion and migration assays were used to investigate the role of HOTTIP in the regulation of biological behaviors of GC cells. Results HOTTIP expression was remarkably increased in GC tissues and cell lines compared with that in the normal control. Clinicopathologic analysis revealed that high HOTTIP expression correlated with larger tumor size, deeper invasion depth, positive lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis identified HOTTIP overexpression as an independent unfavorable prognostic factor in GC patients. Moreover, HOTTIP downregulation by si-HOTTIP transfection impaired GC cell proliferation, promoted cell apoptosis, and reduced cell invasion and migration. Conclusion These findings suggested that HOTTIP may contribute to GC initiation and progression, and would be not only a novel prognostic marker but also a potential therapeutic target for this disease. PMID:27103834

  17. Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancer.

    PubMed

    Cao, Yuan; Shi, Huirong; Ren, Fang; Jia, Yanyan; Zhang, Ruitao

    2017-10-01

    In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion. We further identified and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1 functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b, respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone of these four proteins inhibited EOC cell EMT, migration and invasion. Taken together, our study first revealed a critical role of CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings provide great insights into EOC initiation and progression, and novel potential therapeutic targets and biomarkers for diagnosis and prognosis for EOC. Copyright © 2017. Published by Elsevier Inc.

  18. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

    SciTech Connect

    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang

    2015-12-04

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

  19. Au nanoparticle decorated graphene nanosheets for electrochemical immunosensing of p53 antibodies for cancer prognosis.

    PubMed

    Elshafey, Reda; Siaj, Mohamed; Tavares, Ana C

    2016-04-25

    The accurate quantification of the level of p53 antibodies in serum is crucial for cancer prognosis. We report a novel and sensitive label-free immunosensor based on gold nanoparticles (Au NPs) self-assembled onto electrochemically reduced graphene oxide (ERGO) for the detection of p53 antibodies. An electrografted p-aminophenol organic layer was used to immobilize graphene oxide (GO) onto the surface of screen printed carbon electrodes (SPCE). The Au NP/ERGO hybrid interface provides a large surface area for the effective immobilization of p53 antigens, as well as it ascertains the bioactivity and stability of immobilized p53 antigens. Scanning electron microscope, Raman and X-ray photoelectron spectroscopies were used to monitor the sensor fabrication and cyclic voltammetry was used to quantify the extent of Au NPs' surface coverage by p53 antigens. Square wave voltammetry (SWV) of a [Fe(CN)6](3-/4-) couple was employed to investigate the immunosensor fabrication and to monitor the binding events between p53 antigens and p53 antibodies. Under optimized experimental conditions, the biosensor displayed good sensitivity and specificity. The p53 antibodies were detected in a concentration as low as 0.088 pg mL(-1) with a linear range from 0.1 pg mL(-1) to 10 ng mL(-1). The high sensitivity of the immunosensor may derive from the high loading of p53 antibodies on Au NPs which increases the number of binding events.

  20. Coexistence of MSI with KRAS mutation is associated with worse prognosis in colorectal cancer.

    PubMed

    Hu, Jing; Yan, Wen-Yue; Xie, Li; Cheng, Lei; Yang, Mi; Li, Li; Shi, Jiong; Liu, Bao-Rui; Qian, Xiao-Ping

    2016-12-01

    Kristen rat sarcoma viral oncogene homolog (KRAS) and microsatellite instability (MSI) are prognostic markers of colorectal cancer (CRC). However, the clinical value is still not fully understood, when giving the consideration to both the molecular makers. Five hundred fifty-one patients with CRC were retrospectively assessed by determining their clinicopathological features. KRAS mutations were detected by polymerase chain reaction. MSI, a defect in the mismatch repair (MMR) system, was detected by immunohistochemistry. The prognostic value of KRAS in combination with MSI was studied. Among 551 CRC patients, mutations in KRAS codon 12 and KRAS codon 13 were detected in 34.5% and 10.5% of patients, respectively. Four hundred one tumors were randomly selected to detect for MMR proteins expression. In this analysis, 30 (7.5%) tumors that had at least 1 MMR protein loss were defined as MMR protein-deficient (MMR-D), and the remaining tumors were classed as MMR protein-intact (MMR-I). According to KRAS mutation and MSI status, CRC was classified into 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group4 had the best prognosis. In conclusion, combination status of KRAS and MSI status may be used as a prognostic biomarker for CRC patient, if validated by larger studies.

  1. Data mining and medical world: breast cancers' diagnosis, treatment, prognosis and challenges.

    PubMed

    Oskouei, Rozita Jamili; Kor, Nasroallah Moradi; Maleki, Saeid Abbasi

    2017-01-01

    The amount of data in electronic and real world is constantly on the rise. Therefore, extracting useful knowledge from the total available data is very important and time consuming task. Data mining has various techniques for extracting valuable information or knowledge from data. These techniques are applicable for all data that are collected inall fields of science. Several research investigations are published about applications of data mining in various fields of sciences such as defense, banking, insurances, education, telecommunications, medicine and etc. This investigation attempts to provide a comprehensive survey about applications of data mining techniques in breast cancer diagnosis, treatment & prognosis till now. Further, the main challenges in these area is presented in this investigation. Since several research studies currently are going on in this issues, therefore, it is necessary to have a complete survey about all researches which are completed up to now, along with the results of those studies and important challenges which are currently exist in this area for helping young researchers and presenting to them the main problems that are still exist in this area.

  2. Impact of immunohistological subtypes on the long-term prognosis of patients with metastatic breast cancer.

    PubMed

    Kobayashi, Kokoro; Ito, Yoshinori; Matsuura, Masaaki; Fukada, Ippei; Horii, Rie; Takahashi, Shunji; Akiyama, Futoshi; Iwase, Takuji; Hozumi, Yasuo; Yasuda, Yoshikazu; Hatake, Kiyohiko

    2016-07-01

    Although improved long-term prognoses for patients with metastatic breast cancer (MBC) have been demonstrated, few reports address overall survival (OS) with sufficient follow-up. Furthermore, the relevance of immunohistological subtypes to OS in MBC has not been clarified. We evaluated, retrospectively, the OS of patients who had been initiated on systemic therapy for MBC between 2000 and 2008. The subjects of this study were 527 patients with MBC treated by systemic therapy. The median survival time (MST) was 55.5 months. The MST for each immunohistological subtype was as follows: luminal, 59.9 months; luminal-HER2, not reached; triple-negative, 18.6 months; and HER2-enriched, 49.9 months. According to multivariate analysis, metastasis-free intervals of ≥2 years and treatment with anthracycline for MBC were predictive of better OS. The predictors of shorter OS included disease progression after first-line treatment for MBC, triple-negative, and all histological factors, except papillotubular carcinoma, with liver metastasis, and having three or more initial metastatic sites. The prognosis of the patients with MBC in this series was better than that reported before 2000, which is probably attributable to the use of novel, improved pharmacological agents. For example, luminal-HER2 tumors can be treated using both aromatase inhibitors and trastuzumab. Because of the lower toxicities, it is now possible to administer these agents for longer periods, resulting in better prognoses.

  3. Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer

    PubMed Central

    He, Jun; Jin, Yi; Chen, Yuan; Yao, Hai-Bo; Xia, Ying-Jie; Ma, Ying-Yu; Wang, Wei; Shao, Qin-Shu

    2016-01-01

    Objectives To examine the expression of ALDOB in gastric cancer (GC) tissue and to reveal its potential clinicopathological and prognostic significance. Materials and methods We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed. Results The microarray analysis revealed that ALDOB was downregulated (more than sevenfold) in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC. Conclusion The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC. PMID:27785057

  4. Prognosis value of MGMT promoter methylation for patients with lung cancer: a meta-analysis.

    PubMed

    Chen, Chao; Hua, Haiqing; Han, Chenglong; Cheng, Yuan; Cheng, Yin; Wang, Zhen; Bao, Jutao

    2015-01-01

    The role of MGMT promoter methylation in lung cancer (LC) remains controversial. To clarify the association of MGMT promoter methylation with survival in LC, we performed a meta-analysis of the literature with meta-analysis. Trials were selected for further analysis if they provided an independent assessment of MGMT promoter methylation in LC and reported the survival data in the context of MGMT promoter methylation status. Subgroup analyses were conducted according to the study characteristic. A total of 9 trials, which comprised 859 patients, were included in the meta-analysis. The combined hazard ratio (HR) of 1.27 [95% CI 0.88-1.82; test for heterogeneity P = 0.027] suggests that MGMT promoter methylation has none impact on patient survival. In Stage I-III or younger populations, a significant association was found for MGMT promoter methylation in the prognosis of LC. In addition, the heterogeneity disappeared when the analysis was restricted to Stage I-III LC. Our analysis indicates that MGMT promoter methylation in stage I-III or younger patients was significantly correlated with wore survival. Further study is needed to determine these specific subgroups of LC patients.

  5. Impression of prognosis regarding pathologic stage after preoperative chemoradiotherapy in rectal cancer

    PubMed Central

    Hwang, Kyungyeon; Park, In Ja; Yu, Chang Sik; Lim, Seok-Byung; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Kim, Jin Cheon

    2015-01-01

    AIM: To ascertain pathologic stage as a prognostic indicator for rectal cancer patients receiving preoperative chemoradiotherapy (PCRT). METHODS: Patients with mid- and low rectal carcinoma (magnetic resonance imaging - based clinical stage II or III) between 2000 and 2009 and treated with curative radical resection were identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence-free survival (RFS) was examined according to pathologic stage and addition of adjuvant treatment. RESULTS: Overall, 894 patients were identified. Of these, 500 patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No-PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6% for Stage I, 83.3% for Stage II, and 72.9% for Stage III. The 5-year RFS for the PCRT group was 95.2% for yp Stage 0, 91.7% for yp Stage I, 73.9% for yp Stage II, and 50.7% for yp Stage III. CONCLUSION: Pathologic stage can predict prognosis in PCRT patients. 5-year RFS is significantly lower among PCRT patients than No-PCRT patients in pathologic stage II and III. These results should be taken into account when considering adjuvant treatment for patients treated with PCRT. PMID:25593475

  6. Overexpression of Rad51 Predicts Poor Prognosis in Colorectal Cancer: Our Experience with 54 Patients

    PubMed Central

    Xu, Feng; Liao, Dian-ying; Xie, Li; Wang, Jin; Luo, Feng

    2017-01-01

    Background Aberrant Rad51 expression is implicated in the progression of human malignancies. However, the role of Rad51 in colorectal cancer (CRC) remains undefined. This study aimed to establish a relationship between Rad51 and clinicopathologic features of CRC. Methods We retrospectively examined the paraffin-embedded tissue samples obtained from 54 patients with CRC who had received surgical therapies at our institution during 2006–2008. Rad51 expression in adenocarcinoma, paracancerous tissue, and normal colonic tissue was determined by immunohistochemistry. The correlation between Rad51 immunoreactivity and clinicopathologic features of these patients was evaluated. Results Rad51 immunoreactivity was detected in 67% of adenocarcinoma, 48% of paracancerous tissue, and 27% of normal colonic mucosa. Rad51 expression in adenocarcinoma was significantly higher than normal colonic tissue (p < 0.05). Rad51 was also overexpressed in poorly differentiated tumors and tumor samples from patients with lymph node metastasis (p < 0.05). Patients with Rad51 overexpression had a 69% two-year survival, 49% three-year survival, and 16% five-year survival, considerably worse than patients with negative Rad51 expression (p < 0.05). Conclusion Our data suggest that Rad51 overexpression is correlated with malignant phenotypes of CRC and may predict poor prognosis for these patients. PMID:28099437

  7. CHIP involves in non-small cell lung