Exploring the pathogenesis of renal cell carcinoma: pathway and bioinformatics analysis of dysregulated genes and proteins

Biol Chem. 2009 Feb;390(2):125-35. doi: 10.1515/BC.2009.013.

Abstract

We recently identified a group of proteins which are dysregulated in renal cell carcinoma (RCC). In this study, we performed bioinformatics and pathway analysis of these proteins. Proteins were mapped to gene ontology biological processes. The upregulated proteins tend to cluster in processes, such as cancer initiation and progression. In addition, we identified a number of pathways that are significantly enriched in RCC. Some of these are 'common' pathways which are dysregulated in many cancers, but we also identified a number of pathways which were not previously linked to RCC. In addition to their potential prognostic values, many of these pathways have a potential as therapeutic targets for RCC. To verify our findings, we compared our proteins to a pool of datasets from published reports. Although there were only a minimal number of common proteins, there was a significant overlap between the identified pathways in the two groups. Moreover, out of 16 individually discovered genes identified by a literature search, 10 were found to be related to our dysregulated pathways. We also verified the upregulation of the mammalian target of rapamycin signaling pathway in RCC by immunohistochemistry. Finally, we highlight the potential clinical applications of pathway analysis in kidney cancer.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / physiopathology
  • Computational Biology*
  • Databases, Protein*
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / physiopathology
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Reference Standards
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • TOR Serine-Threonine Kinases

Substances

  • Biomarkers, Tumor
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases