Abstract
While considerable research into colorectal cancer (CRC) has implicated many genetic alterations that trigger the disease and sustain its progression, there are few well-validated, clinically useful molecular biomarkers of CRC. The observation that cancer is highly diverse across individual tumors is manifested at the molecular level by concomitantly diverse patterns of gene expression. However, while analysis of gene expression has been used to identify candidate biomarkers of cancer, such biomarkers frequently do not cross validate well on independent datasets and this has raised legitimate concerns regarding the usefulness of gene expression based markers. It is has been postulated that by integrating the functional information of gene products into the approach, networks of mechanistically related gene products may be identified and used to develop more robust biomarkers. Many such approaches focus on established signaling pathways for this purpose; however, pathways consisting of a few proteins interacting in a serial fashion oversimplify, and provide inadequate models for, a complex phenotype (e.g. CRC) mediated by a constellation of interacting gene products. Here, we discuss several integrative techniques based on cellular networks (protein–protein interactions) and incorporation of lower-coverage, but functionally relevant proteomic data, and show the power these techniques hold for prioritizing disease genes for biomarker discovery and biological verification of function.
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Acknowledgments
The research presented here was supported, in part, by National Institutes of Health Grants UL1-RR024989 from the National Center for Research Resources (Clinical and Translational Science Awards), P30-CA043703 from the Case Western Reserve University Cancer Center Proteomics Core, and T32-GM008803 from the NIGMS (Institutional National Research Service Award). This work was also supported, in part, by NSF CAREER Award CCF-0953195.
All inquiries related to SASSy, X-TALKER, or CRANE should be directed to john.schenkel@neoproteomics.net.
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Koyuturk, M., Nibbe, R. (2015). Omics and Biomarkers Development for Intestinal Tumorigenesis. In: Yang, V., Bialkowska, A. (eds) Intestinal Tumorigenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-19986-3_12
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DOI: https://doi.org/10.1007/978-3-319-19986-3_12
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