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Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities

  1. Author:
    Vasaikar, Suhas
    Huang, Chen
    Wang, Xiaojing
    Petyuk, Vladislav A.
    Savage, Sara R.
    Wen, Bo
    Dou, Yongchao
    Zhang, Yun
    Shi, Zhiao
    Arshad, Osama A.
    Gritsenko, Marina A.
    Zimmerman, Lisa J.
    McDermott, Jason E.
    Clauss, Therese R.
    Moore, Ronald J.
    Zhao, Rui
    Monroe, Matthew E.
    Wang, Yi-Ting
    Chambers, Matthew C.
    Slebos, Robbert J. C.
    Lau, Ken S.
    Mo, Qianxing
    Ding, Li
    Ellis, Matthew
    Thiagarajan,Mathangi
    Kinsinger, Christopher R.
    Rodriguez, Henry
    Smith, Richard D.
    Rodland, Karin D.
    Liebler, Daniel C.
    Liu, Tao
    Zhang, Bing
    Ellis, Matthew J. C.
    Bavarva, Jasmin
    Borucki, Melissa
    Elburn, Kimberly
    Hannick, Linda
    Vatanian, Negin
    Payne, Samuel H.
    Carr, Steven A.
    Clauser, Karl R.
    Gillette, Michael A.
    Kuhn, Eric
    Mani, D. R.
    Cai, Shuang
    Ketchum, Karen A.
    Thangudu, Ratna R.
    Whiteley, Gordon A.
    Paulovich, Amanda
    Whiteaker, Jeff
    Edward, Nathan J.
    Madhavan, Subha
    McGarvey, Peter B.
    Chan, Daniel W.
    Shih, Ie-Ming
    Zhang, Hui
    Zhang, Zhen
    Zhu, Heng
    Skates, Steven J.
    White, Forest M.
    Mertins, Philip
    Pandey, Akhilesh
    Slebos, Robert J. C.
    Boja, Emily
    Hiltke, Tara
    Kinsinger, Christopher R.
    Mesri, Mehdi
    Rivers, Robert C.
    Stein, Stephen E.
    Fenyo, David
    Ruggles, Kelly
    Levine, Douglas A.
    Oberti, Mauricio
    Rudnick, Paul A.
    Snyder, Michael
    Tabb, David L.
    Zhao, Yingming
    Chen, Xian
    Ransohoff, David F.
    Hoofnagle, Andrew
    Sanders, Melinda E.
    Wang, Yue
    Davies, Sherri R.
    Townsend, R. Reid
    Watson, Mark

  2. Author Address

    Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA.Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN 37232 USA.Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA.Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA.Washington Univ, McDonnell Genome Inst, Forest Pk Ave,Campus Box 8501, St Louis, MO 63108 USA.Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21702 USA.NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97221 USA.Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL 33612 USA.
    1. Year: 2019
    2. Date: May 2
    3. Epub Date: 2019 04 25
  2. Journal: CELL
  3. CELL PRESS,
    1. 177
    2. 4
    3. Pages: 1035-1049.e19
  5. Type of Article: Article
  6. ISSN: 0092-8674
  1. Abstract:

    We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2019.03.030
  3. PMID: 31031003
  4. View record in Web of Science®
  5. WOS: 000466843000021

Library Notes

  1. Fiscal Year: FY2018-2019
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