Identification of key genes and microRNA regulatory network in development and progression of urothelial bladder carcinoma

Background: Bladder cancer as other cancers contains multiple dynamic alterations in progression. Theoretically, large number of genes participates in cancer progression. In the present study, the interconnections of genesets defined by Gene Set Enrichment Analysis (GSEA) and tumor histopathological stages were characterized. In addition, the outcomes with genesets were discussed in bladder cancer. Methods: Transcriptome data from 411 tissues of urothelial bladder carcinoma and 19 samples from adjacent tissues were retrieved from The Cancer Genome Atlas (TCGA) database. Single-sample GSEA (ssGSEA), cluster analysis of geneset enrichment scores and genesets as indicators in prognosis were applied to elucidate the correlations between genesets and bladder cancer progression. Results: Chemical and genetic perturbations (CGP), canonical pathways (CP), CP:BIOCARTA (BioCarta gene sets), CP:KEGG (KEGG gene sets) and CP:REACTOME (Reactome gene sets) in C2 collection, upstream cis-regulatory motifs serum response factor (SRF) in C3 collection, KRAS in C6 collection and C8+ T cells in C7 collection were observed as enriched by ssGSEA. The cluster 2 identified from cluster analysis shows a more immune active microenvironment which tended to increase in stage II and decreased in stage IV indicating the crucial role in bladder cancer progression. miR-450, miR-518s, transcription factor PAX3, KRAS and PTEN were potential markers for outcomes of urothelial bladder carcinoma. Activating tumor immune microenvironment had deteriorated prognosis of patients with bladder cancer. Conclusions: Our findings demonstrated that activating tumor immune microenvironment is a negative factor for outcomes of urothelial bladder carcinoma. These data provided a potential combination strategy for patients with bladder cancer.

Automated summary

This study investigated the relationship between genesets and histopathological stages of bladder cancer using GSEA, identifying that activating tumor immune microenvironment is a negative factor for outcomes of urothelial bladder carcinoma, which provides potential combination strategy for patients with bladder cancer.