The Role of Alternative Splicing Factors, DDB2-Related Ageing and DNA Damage Repair in the Progression and Prognosis of Stomach Adenocarcinoma Patients.

Abstract

DNA damage response is a key signal transduction pathway in triggering ageing and tumor progression. Abnormal alternative splicing (AS) is associated with tumors and ageing. However, the role of AS factors associated with DNA damage repair and ageing in stomach adenocarcinoma (STAD) remains unclear. We downloaded the percentage of splicing (PSI) values for AS in STAD from the TCGA SpliceSeq database. The PSI values of DNA repair gene AS events were integrated with STAD patient survival data for Cox regression analysis. The prediction model for the overall survival (OS) was constructed by the clinical traits. The tumor immune microenvironment was analyzed by CIBERSORT and ESTIMATE. We detected 824 AS events originating from 166 DNA repair genes. Cox regression analysis provided 21 prognostic AS events connected with OS statistically, and a prognostic prediction model was constructed. The expression of these AS factors was higher in STAD tumors. DDB2 high senescence levels were associated with active immune responses and better survival in STAD patients. We built a novel prognostic model founded on DNA repair genes with AS events and identified that DDB2 may be a potential biomarker to apply in clinics.