Identification of differentially expressed genes and biological pathways in bladder cancer

Abstract

The purpose of the present study was to identify key genes and investigate the related molecular mechanisms of bladder cancer (BC) progression. From the Gene Expression Omnibus database, the gene expression dataset GSE7476 was downloaded, which contained 43 BC samples and 12 normal bladder tissues. GSE7476 was analyzed to screen the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs using the DAVID database, and a protein‑protein interaction (PPI) network was then constructed using Cytoscape software. The results of the GO analysis showed that the upregulated DEGs were significantly enriched in cell division, nucleoplasm and protein binding, while the downregulated DEGs were significantly enriched in 'extracellular matrix organization', 'proteinaceous extracellular matrix' and 'heparin binding'. The results of the KEGG pathway analysis showed that the upregulated DEGs were significantly enriched in the 'cell cycle', whereas the downregulated DEGs were significantly enriched in 'complement and coagulation cascades'. JUN, cyclin‑dependent kinase 1, FOS, PCNA, TOP2A, CCND1 and CDH1 were found to be hub genes in the PPI network. Sub‑networks revealed that these gene were enriched in significant pathways, including the 'cell cycle' signaling pathway and 'PI3K‑Akt signaling pathway'. In summary, the present study identified DEGs and key target genes in the progression of BC, providing potential molecular targets and diagnostic biomarkers for the treatment of BC.

Keywords: bioinformatics analysis; bladder cancer; differentially expressed genes; enrichment analysis; protein-protein interaction.

Figure 1.

Volcano plot of the DEGs. The abscissa represents logFC and the ordinate represents-log₁₀ (P-value). The red and green dots indicate DEGs, while the black dots represent genes that are not differentially expressed between bladder cancer and healthy control tissues. Red, upregulation; green, downregulation. DEG, differentially expressed gene; FC, fold-change.

Figure 2.

The top 15 enriched Gene Ontology terms of upregulated (A) and downregulated (B) differentially expressed genes. DEG, differentially expressed gene.

Figure 3.

The top five enriched pathways of upregulated (A) and downregulated (B) differentially expressed genes. DEG, differentially expressed gene.

Figure 4.

Top 3 modules from the PPI network. (A) The top 3 significant modules were selected. (B) Module 1 of DEGs from the PPI network; (C) module 2 of DEGs from the PPI network; and (D) module 3 of DEGs from the PPI network. PPI, protein-protein interaction; DEG, differentially expressed gene.