Significance and Mechanisms Analyses of RB1 Mutation in Bladder Cancer Disease Progression and Drug Selection by Bioinformatics Analysis

Abstract

BACKGROUND: Bladder cancer is still a disease of significant morbidity and mortality. In bladder cancer, RB1 is one of the most common mutant genes. METHODS: In this study, we explored the Genomics of Drug Sensitivity in Cancer (GDSC) database for drug sensitivity. The latest TCGA data were downloaded for analysis. To deal with functional enrichment analysis, GSEA, KEGG and GO were used. Prognostic analyses have been carried out using the GEPIA online tool. RESULTS: Results from the GDSC database showed that bladder cancer cells with RB1 mutation are more resistant to Dactolisib, MK-2206 and GNE-317. RB1 mutation was found in 25%bladder cancer patients. Patients with RB1 mutation often had lower RB1 mRNA expression level and higher histologic grade. In addition, we identified 999 differentially expressed genes in both groups. Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, cell proliferation and cancer related pathways. There were strong correlations between WT1, GPR37, CHRM2 and EZH2 expression levels and the prognosis. CONCLUSIONS: In all, the significance of RB1 mutation in disease progression and drug selection in bladder cancer was suggested by our results, and multiple genes and pathways related to such a program were identified.