Autoantibodies in cancer: prognostic biomarkers and immune activation

The development of proteomic technologies that display a wide variety of antigenic structures has led to the identification of autoantibodies to cancer-derived tumor antigens. These autoantibodies have been detected in sera from patients with multiple cancer types, and are being evaluated as biomarkers for early cancer detection. It is not known whether these antibodies also contribute to active immune surveillance or even tumorigenicity of developing tumors. Here, we review which tumor antigen-specific antibodies are prognostic biomarkers of cancer outcome, and emerging proteomic methods for the isolation and cloning of these antibodies for potential molecular diagnostics and therapeutics.     

miR‐4709 overexpression facilitates cancer proliferation and invasion via downregulating NR3C2 and is an unfavorable prognosis factor in colon adenocarcinoma

To date, microRNA‐4709 (miR‐4709) has not been studied in colon adenocarcinoma (COAD) on the basis of experiments. In our study, we aimed to investigate the biological roles and clinical significance of miR‐4709 in COAD. The expression difference between miR‐4709 and NR3C2 was measured based on The Cancer Genome Atlas database and cells. Kaplan‐Meier and logrank tests were applied to determine the overall survival (OS) differences according to the miR‐4709 and NR3C2 expression levels. To measure whether the miR‐4709 level was associated with COAD cell growth, migration, and invasion, we respectively conducted 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, wound healing, and transwell assays. A luciferase reporter assay was applied to confirm the relationship between miR‐4709 and its predicted target. High expression of miR‐4709 was found in COAD tissues and cells. The OS rate in the miR‐4709 low expression group was significantly higher than that in the miR‐4709 high expression group. Univariate and multivariate analyses exhibited that miR‐4709 expression was an independent adverse prognostic factor. Exogenous miR‐4709 overexpression promoted proliferation, migration, and invasion of LOVO and SW480 cells. Bioinformatics analysis and luciferase assay demonstrated that miR‐4709 directly binds to the 3′‐untranslated region of NR3C2. NR3C2 was lowly expressed in COAD and high expression of NR3C2 had a better prognosis compared with that in the low expression of NR3C2. Correlation analysis showed that there is a close association between the level of expression of NR3C2 and miR‐4709. Accordingly, miR‐4709 may function as an oncogene in COAD and provide a preclinical proof for candidate management to target new miR‐4709‐NR3C2 signaling for COAD therapy.     

Low expression of Beclin 1, associated with high Bcl-xL,predicts a malignant phenotype and poor prognosis of gastric cancer

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.     

Call for Papers Special Issue on “Biomarkers for Diseases”

正The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in June of 2015)on the topic of"Biomarkers for Diseases".As an emerging index,disease biomarkers have demonstrated the potential application in diagnosis and prognosis.The detection of the disease indicators at molecular level,DNA,RNA,protein or metabolites,could gain highly     

Identification of a four immune-related genes signature based on an immunogenomic landscape analysis of clear cell renal cell carcinoma

Renal clear cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, which has strong immunogenicity. A comprehensive study of the role of immune-related genes (IRGs) in ccRCC is of great significance in finding ccRCC treatment targets and improving patient prognosis. In this study, we comprehensively analyzed the expression of IRGs in ccRCC based on The Cancer Genome Atlas datasets. The mechanism of differentially expressed IRGs in ccRCC was analyzed by bioinformatics. In addition, Cox regression analysis was used to screen prognostic related IRGs from differentially expressed IRGs. We also identified a four IRGs signature consisting of four IRGs (CXCL2, SEMA3G, PDGFD, and UCN) through lasso regression and multivariate Cox regression analysis. Further analysis results showed that the four IRGs signature could effectively predict the prognosis of patients with ccRCC, and its predictive power is independent of other clinical factors. In addition, the correlation analysis of immune cell infiltration showed that this four IRGs signature could effectively reflect the level of immune cell infiltration of ccRCC. We also found that the expression of immune checkpoint genes CTLA-4, LAG3, and PD-1 in the high-risk group was higher than that in the low-risk group. Our research revealed the role of IRGs in ccRCC, and developed a four IRGs signature that could be used to evaluate the prognosis of patients with ccRCC, which will help to develop personalized treatment strategies for patients with ccRCC and improve their prognosis. In addition, these four IRGs may be effective therapeutic targets for ccRCC.     

Nomograms-based prediction of overall and cancer-specific survivals for patients with chromophobe renal cell carcinoma

This study built and tested two effective nomograms for the purpose of predicting cancer-specific survival and overall survival of chromophobe renal cell carcinoma (chRCC) patients. Multivariate Cox regression analysis was employed to filter independent prognostic factors predictive of cancer-specific survival and overall survival, and the nomograms were built based on a training set incorporating 2901 chRCC patients in a retrospective study (from 2004 to 2015) downloaded from the surveillance, epidemiology, and end results (SEER) database. The nomograms were verified on a validation cohort of 1934 patients, subsequently the performances of the nomograms were examined according to the receiver operating characteristic curve, calibration curves, the concordance (C-index), and decision curve analysis. The results showed that tumor grade, AJCC and N stages, race, marital status, age, histories of chemotherapy, radiotherapy and surgery were the individual prognostic factors for overall survival, and that AJCC, N and SEER stages, histories of surgery, radiotherapy and chemotherapy, age, tumor grade were individual prognostic factors for cancer-specific survival. According to C-indexes, receiver operating characteristic curves, and decision curve analysis outcomes, the nomograms showed a higher accuracy in predicting overall survival and OSS when compared with TNM stage and SEER stage. All the calibration curves were significantly consistent between predictive and validation sets. In this study, the nomograms, which were validated to be highly accurate and applicable, were built to facilitate individualized predictions of the cancer-specific survival and overall survival to patients diagnosed with chRCC between 2004 and 2015.