Significance of CTNNB1 Mutation in Cellular Process, Prognosis, and Drug Selection in Gastric Cancer

Abstract Background: Numerous studies have reported that CTNNB1 mutant is a frequently mutated gene found in gastric cancer (GC), making this a valuable biomarker for GC. However, the underling mechanism of CTNNB1 regulating GC remains unknown.Aim of the study: To identify the significance of the CTNNB1 mutation in the prognosis and drug selection of GC, evaluate important genes and pathways that are involved in the pathogenesis of GC. Methods: Data sets were downloaded from the Cancer Genome Atlas (TCGA)-STAD. CTNNB1 mutation and drug sensitivity analysis based on GDSC database. CTNNB1 wild group and mutant group analyzed by GSEA enrichment. The differentially expressed genes (DEGs) were identified by LIMMA package for further GO and KEGG analysis. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. Results: The CTNNB1 mutation is found in 8% of GC patients. Patients with CTNNB1 mutations had better prognosis on overall survival and disease-free survival. GC cells with CTNNB1 mutation are sensitive to Nutlin-3a. In total 727 genes were identified as DEGs. GO and KEGG analysis suggested that DEGs were significantly enriched in categories associated with cell differentiation and immune response, digestion related pathways and multiple signal transduction related pathways. Top three significant modules of genes in the PPI network were identified and analyzed. Conclusions: Our results indicated that multiple genes and pathways may play a key role in GC patients with CTNNB1 mutation, implicated these factors as possible targets for future therapeutic strategies in patients with GC.