Bioinformatics analysis of differential genes between muscular and non-muscle invasive bladder cancer

Abstract:

Objective：To screen key genes in the progression of bladder cancer（BC） and explore their biological effects，providing a basis for finding potential therapeutic targets. Methods：The data of BC patients were retrieved from the GEO database. Differentially expressed genes（DEGs） of muscular invasive bladder cancer（MIBC） and non-muscle invasive bladder cancer（NMIBC） were screened by R software；the cluster Profiler software package was used for DEGs function annotation and path analysis. The STRING online database combined with Cytoscape software was used to analyze protein-protein interaction（PPI） network and screen central genes and key templates. TCGA database of GEPIA online analysis tool was used for prognostic analysis and screening key genes. The expression level of key genes was validated in Oncomine Tumor Database and imported into SPSS 22.0 for statistical analysis. The expression level of key genes in different invasive BC were verified based on the immunohistochemical results of The HUMAN PROTEIN ATLAS. Results：A total of 193 DEGs were screened，among which 116 were up-regulated and 77 were down-regulated，which were mainly involved in the biological processes of extracellular matrix tissues，cellular component composition，molecular functions，and signaling pathways such as MAPK. A total of 65 central genes were obtained after PPI analysis，and the prognostic analysis of central genes showed that expression levels of six key genes were significantly correlated with the overall survival time of BC patients，with statistically significant differences（P<0.01）. Oncomine database validation showed that five key genes of CXCL12，ANXA5，ACTA2，TAGLN and COL6A2，were significantly up-regulated in MIBC，while PPARG was significantly down-regulated in MIBC（P<0.05）. Conclusion：Changes of biological effects of extracellular matrix，MAPK pathway and six key genes（CXCL12，ANXA5，ACTA2，TAGLN，COL6A2 and PPARG） on tumor invasion may become potential therapeutic targets to inhibit the progression of BC.