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

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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 and development of colorectal cancer is a multistep 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 messenger RNA (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.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, New York Medical College, 15 Dana Road, Valhalla, NY, 10595, USA

    Barbara B. Doonan, Evelien Schaafsma, John T. Pinto, Joseph M. Wu & Tze-chen Hsieh

  2. Department of Cell Biology and Anatomy, New York Medical College, 15 Dana Road, Valhalla, NY, 10595, USA

    Evelien Schaafsma

Authors
  1. Barbara B. Doonan
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  2. Evelien Schaafsma
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  3. John T. Pinto
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  4. Joseph M. Wu
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  5. Tze-chen Hsieh
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Contributions

ES researched and performed the Oncomine query under supervision of TCH and wrote the first draft of the manuscript. ES received a Master of Science in Cell Biology, New York Medical College, Valhalla, NY. TCH, ES, and JMW designed the research, analyzed the data, and wrote the early drafts of the manuscript. BD and JTP edited and corrected the manuscript. BBD drafted this manuscript and corresponded with Dr. John Harbell at IVA for consideration of publication of this manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Barbara B. Doonan.

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Funding

This research was made possible with personal contributions for research support to TCH. The authors declare that the funding source has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Editor: Tetsuji Okamoto

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Doonan, B.B., Schaafsma, E., Pinto, J.T. et al. Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma. In Vitro Cell.Dev.Biol.-Animal 53, 575–578 (2017). https://doi.org/10.1007/s11626-017-0174-x

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  • DOI: https://doi.org/10.1007/s11626-017-0174-x

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