Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer
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RESEARCH ARTICLE
Open Access
Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer Chao Wu, Zuowei Wu and Bole Tian*
Abstract Background: Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. Methods: Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. Results: Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p < 0.001) than the low-risk group, in both the primary set and the validation set. The concordance index (C-index) was calculated to evaluate the predictive performance of the nomogram were respectively in the primary set [0.696 (0.608–0.784)] and the validation set [0.682 (0.606–0.758)]. Additionally, gene set enrichment Analysis discovered several meaningful enriched pathways. Conclusion: Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC. Keywords: Pancreatic cancer, Prognostic model, TCGA, Biomarkers, Survival, Nomogram
Introduction Pancreatic cancer is a malignant neoplasm with a high incidence and mortality worldwide [1, 2]. The near inability to diagnose early stage pancreatic cancer results in missed chances of surgery, which is the main method of cure for PC patients [3]. Additionally, therapeutic schedules for advanced stage pancreatic cancer have * Correspondence: [email protected] Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
made little progress in past decades due to its characteristic insensitivity to radiotherapy and chemotherapy [4]. Furthermore, some of its characteristic proteins are also expressed in chronic pancreatitis, decreasing the biomarker specificity for the diagnosis of PC [5]. Thus, neither the diagnosis nor the therapeutic schedule of pancreatic cancer is satisfactory at present. Therefore, there is an urgent need to identify a novel advanced biomarker for diagnosing and developing therapies for PC patients to
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