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.

Assessment of molecular mechanisms and potential biomarkers in bladder urothelial carcinoma

“…Annotation of upregulated genes to cell cycle pathway and cell cycle related GO-BP terms might indicate the increased mitosis and cell division in bladder urothelial carcinoma cells. The upregulation of genes in cell division terms is consistent with previous report showing enrichment of differentially expressed upregulated genes in cell division and cell cycle related terms in bladder cancer [5]. According to KEGG pathway and GO-BP term annotations, downregulated genes in bladder urothelial carcinoma cells mostly annotated to adhesion, ECM-receptor interaction, cardiomyopathy related pathways, muscle related and circulatory system related GO-BP terms (Table 2).…”

“…The increased expression of genes in bladder cancer found to be annotated to negative regulation apoptotic process, salmonella infection, amoebiasis, malaria pathways and rheumatoid arthritis pathways, while downregulated genes were annotated to oxidative phosphorylation, taurine and hypotaurine metabolism, vitamin digestion and absorption, arthritis and vibrio cholerae infection pathways [7]. Enrichment of upregulated genes in cell division and protein binding, enrichment of downregulated genes in extracellular matrix organization and complement and coagulation cascades was also reported [5]. Studies with TCGA datasets of bladder cancer mainly focus on genomic analysis of DNA alterations, including variations and mutations, and related pathways [8][9][10][11].…”

“…To identify molecular mechanisms that were altered in bladder urothelial carcinoma, upregulated and downregulated differentially expressed genes were annotated to GO-BP terms and KEGG pathway terms. Upregulated genes mainly annotated to cell tumor and control samples to reveal altered gene expression mechanisms of bladder urothelial carcinoma [5,6]. The increased expression of genes in bladder cancer found to be annotated to negative regulation apoptotic process, salmonella infection, amoebiasis, malaria pathways and rheumatoid arthritis pathways, while downregulated genes were annotated to oxidative phosphorylation, taurine and hypotaurine metabolism, vitamin digestion and absorption, arthritis and vibrio cholerae infection pathways [7].…”

Upregulation of ASPM, BUB1B and SPDL1 in tumor tissues predicts poor survival in patients with pancreatic ductal adenocarcinoma

“…Furthermore, hormone inhibitors, such as angiotensin system inhibitors were applied to improve the prognosis of PDAC (27). KEGG pathway analysis demonstrated that the upregulated genes were predominantly involved in 'ECM-receptor interaction' and the 'cGMP-PKG signaling pathway', which has been identified as a key signaling pathway in different types of cancer, including bladder cancer (28). A total of 18 hub genes were discovered following construction of the PPI network, in which three key genes (ASPM, BUB1B and SPDL1) were demonstrated to be enriched in the cell cycle biological processes/pathways, and were significantly associated with both shorter OS and DFS in patients with PDAC.…”

Identification of key gene biomarkers and pathways related to Dent disease in CLCN5 knockout mice by bioinformatics analysis

“…We analyzed the raw data by GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/). Statistically significant DEGs were defined with P value <0.01 and a |log2 fold change (FC)| ≥1 as the thresholds described in the references [32][33][34] .…”