Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma

Barbara B. Doonan, Evelien Schaafsma, John T. Pinto, Joseph M. Wu, Tze-chen Hsieh
2017 In vitro Cellular & Developmental Biology-Animal  
T. (2017). Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma. ABSTRACT Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene), has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis
more » ... nd development of colorectal cancer is a multi-step process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI) and CpG island methylator (CIMP). Targets of resveratrol, including a high affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies might be gleaned using publicly available databases. A web-based microarray gene expression data-mining platform, Oncomine, was selected and used to determine whether QR2 may serve as a mechanistic and functional biotarget within the various CRC etiologies. We found that QR2 mRNA is overexpressed in CRC characterized by CIN, particularly in cells showing a positive KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation, as well as by the MSI but not the CIMP phenotype. Mining of Oncomine revealed an excellent correlation between QR2 mRNA expression and certain CRC etiologies. Two resveratrol associated genes, adenomatous polyposis coli (APC) and TP53 found in CRC were further mined, using cBio portal and Colorectal Cancer Atlas which predicted a mechanistic link to exist between resveratrol→QR2/TP53→CIN. Multiple web-based data mining can provide valuable insights which may lead to hypotheses serving to guide clinical trials and design of therapies for enhanced disease prognosis and patient survival. This approach resembles a BioGPS, a capability for mining Web-based databases that can elucidate the potential links between compounds to provide correlations of these interactions with specific diseases.
doi:10.1007/s11626-017-0174-x pmid:28646291 fatcat:qbqiul3wk5e4fknqcj3vo5mm5e