Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma
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(2020) 18:236
RESEARCH
Open Access
Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma Yaqi Qu1, Yujia Chen2, Le Zhang3 and Lifei Tian1*
Abstract Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. Reliable prognostic biomarkers are needed to guide clinical practice. Methods: Comprehensive gene expression with alternative splicing (AS) profiles for each patient was downloaded using the SpliceSeq database from The Cancer Genome Atlas. Cox regression analysis was conducted to screen for prognostic AS events. The R package limma was used to screen differentially expressed genes (DEGs) between normal and tumor samples in the COAD cohort. A Venn plot analysis was performed between DEGs and prognostic AS events, and the DEGs that co-occurred with prognostic AS events (DEGAS) were identified. The top 30 mostconnected DEGAS in protein–protein interaction analysis were identified through Cox proportional hazards regression to establish prognostic models. Results: In total, 350 patients were included in the study. A total of 22,451 AS events were detected, of which 2004 from 1439 genes were significantly associated with survival time. By overlapping these 1439 genes with 6455 DEGs, 211 DEGs with AS events were identified. After the construction of the protein–protein interaction network, the top 30 hub genes were included in a multivariate analysis. Finally, a risk score based on 12 genes associated with overall survival was established (P < 0.05). The area under the curve was 0.782. The risk score was an independent predictor (P < 0.001). Conclusions: By exploring survival-associated AS events, a powerful prognostic predictor consisting of 12 DEGAS was built. This study aims to propose a novel method to provide treatment targets for COAD and guide clinical practice in the future. Keywords: Colon adenocarcinoma, Alternative splicing, Prognostic risk score, Differentially expressed genes
Introduction Colorectal cancer (CRC) is the third most common cancer and the third most common cause of tumor-related death. The incidence and mortality rate of CRC have increased dramatically over the past three decades in China because of changes in lifestyle factors [1]. CRC includes colon * Correspondence: [email protected] 1 Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, China Full list of author information is available at the end of the article
adenocarcinoma (COAD) and rectal adenocarcinoma. COAD is one of the main causes of cancer-associated deaths worldwide [2]. Approximately 41% of all CRCs occur in the proximal colon, with approximately 22% involving the distal colon and 28% involving the rectum. The prognosis of COAD is less than satisfactory; over 1.8 million new COAD cases and 881,000 deaths occurred in 2018 [3]. Therefore, there is a need to discover new molecules capable of identifying pre-cancerous lesions.
© The Author(s). 2020 Open Acce
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