Identification Of Hub Genes, microRNAs And Key Pathways Associated With Bladder Cancer

Bladder cancer is carcinoma of epithelial cells of urinary bladder. It is classified into muscle-invasive bladder cancer and non-muscle-invasive bladder cancer based on alteration of genes like Hras, deletion of chromosome ۹ and a point mutation in FGFR۳.Purpose:In this study we aimed to identify genes and microRNAs important in pathogenesis of Bladder cancer. Methods:Gene expression and microRNA profile of GSE۴۰۳۵۵ was available from Gene Expression Omnibus database. ۸ samples of bladder tissue from healthy people, ۸ samples from patients with Low grade and ۸ samples from patients with High grade Bladder Cancer were selected from dataset. Dataset was analyzed with GEO۲R tools to calculate differentially expressed genes and differentially expressed microRNAs. P-values of < ۰.۰۵ and a | log (fold change)| > ۲.۵ in di↵erentially expressed genes and a | log (fold change)| > ۲.۰ in di↵erentially expressed microRNAs were applied to identify significant differentially expressed genes and di↵erentially expressed microRNAs. We established a protein-protein interaction network of differentially expressed genes through STRING database and used Gephi software to select hub genes. We used Toppgene database for gene ontology and microRNA target prediction. Cytoscape software was used to identify hub microRNA.Results:Total ۱۳۹۸ di↵erentially expressed genes were identified, ۱۲۴۴ nodes and ۹۰۱۴ edges were established based on Protein – Protein Interaction network. ۵ hub genes based on degree (IGF۱, VEGFA, CD۴۴, FOS, ESR۱) and ۵ mirna hubs (mir-۱, mir-۲۹c, mir-۲۹a, mir-۲۹b, mir-۵۷۶) were identified. Significant gene ontologies from Pathway included Ensemble of genes encoding core extracellular matrix including extracellular matrix glycoproteins, collagens and proteoglycans and extracellular matrix organization. Conclusion:In this study, we investigated genes and microRNA effective in pathogenesis of bladder cancer, which can help identifying biomarkers for early diagnosis and new treatment methods.

کلیدواژه ها:

Bladder Cancer ، Biomarkers ، Transcriptomics ، microRNA ، Hub Genes