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Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities

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Item Type:Article
Title:Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities
Creators Name:Vasaikar, S. and Huang, C. and Wang, X. and Petyuk, V.A. and Savage, S.R. and Wen, B. and Dou, Y. and Zhang, Y. and Shi, Z. and Arshad, O.A. and Gritsenko, M.A. and Zimmerman, L.J. and McDermott, J.E. and Clauss, T.R. and Moore, R.J. and Zhao, R. and Monroe, M.E. and Wang, Y.T. and Chambers, M.C. and Slebos, R.J.C. and Lau, K.S. and Mo, Q. and Ding, L. and Ellis, M. and Thiagarajan, M. and Kinsinger, C.R. and Rodriguez, H. and Smith, R.D. and Rodland, K.D. and Liebler, D.C. and Liu, T. and Zhang, B.
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.
Keywords:Colon Cancer, Proteomics, Proteogenomics, Tumor Antigen, Immune Evasion, Glycolysis, Drug Targets, Biomarkers, RB1, SOX9
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:177
Number:4
Page Range:1035-1049
Date:2 May 2019
Additional Information:Philipp Mertins is a member of the Clinical Proteomic Tumor Analysis Consortium.
Official Publication:https://doi.org/10.1016/j.cell.2019.03.030
PubMed:View item in PubMed

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