title: Exploring the pathogenesis of renal cell carcinoma: pathway and bioinformatics analysis of dysregulated genes and proteins.
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.
authors.affiliation: Department of Laboratory Medicine and the Keenan Research Center in the Li Ka Shing Knowledge Institute, St. Michael's Hospital Toronto, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5B 1W8, Canada.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: Youssef
authors.initials: Y
authors.lastname: Youssef
authors.forename: Tsz-fung F
authors.initials: TF
authors.lastname: Chow
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
authors.forename: Leroi V
authors.initials: LV
authors.lastname: DeSouza
authors.forename: R John
authors.initials: RJ
authors.lastname: Honey
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Pace
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000503:physiopathology; D019295:Computational Biology; D030562:Databases, Protein; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000503:physiopathology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D014408:Biomarkers, Tumor; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases