Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis

Mol Med Rep. 2014 Oct;10(4):1746-52. doi: 10.3892/mmr.2014.2396. Epub 2014 Jul 18.

Abstract

The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T‑tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.

MeSH terms

  • Computational Biology*
  • Databases, Genetic
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Up-Regulation
  • Urinary Bladder / metabolism*
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • NF-kappa B
  • NFATC Transcription Factors
  • RNA, Messenger
  • Transcription Factor AP-1
  • Interleukin-10