@article{32198ea0e7be4fc2b40b8b47ff584491,
title = "Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities",
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. A systematic proteogenomic analysis of colon cancer reveals vulnerabilities of potential clinical value inaccessible from genomic assessment alone.",
keywords = "RB1, SOX9, biomarkers, colon cancer, drug targets, glycolysis, immune evasion, proteogenomics, proteomics, tumor antigen",
author = "{Clinical Proteomic Tumor Analysis Consortium} and Suhas Vasaikar and Chen Huang and Xiaojing Wang and Petyuk, {Vladislav A.} and Savage, {Sara R.} and Bo Wen and Yongchao Dou and Yun Zhang and Zhiao Shi and Arshad, {Osama A.} and Gritsenko, {Marina A.} and Zimmerman, {Lisa J.} and McDermott, {Jason E.} and Clauss, {Therese R.} and Moore, {Ronald J.} and Rui Zhao and Monroe, {Matthew E.} and Wang, {Yi Ting} and Chambers, {Matthew C.} and Slebos, {Robbert J.C.} and Lau, {Ken S.} and Qianxing Mo and Li Ding and Matthew Ellis and Mathangi Thiagarajan and Kinsinger, {Christopher R.} and Henry Rodriguez and Smith, {Richard D.} and Rodland, {Karin D.} and Liebler, {Daniel C.} and Tao Liu and Bing Zhang and Ellis, {Matthew J.C.} and Jasmin Bavarva and Melissa Borucki and Kimberly Elburn and Linda Hannick and Negin Vatanian and Payne, {Samuel H.} and Carr, {Steven A.} and Clauser, {Karl R.} and Gillette, {Michael A.} and Eric Kuhn and Mani, {D. R.} and Shuang Cai and Chan, {Daniel W.} and Shih, {Ie Ming} and Hui Zhang and Zhen Zhang and Heng Zhu",
note = "Funding Information: This work was supported by the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) ( U24CA159988 , U24CA210954 , U24CA160019 , and U24CA210955 ) and the Cancer Prevention & Research Institutes of Texas (CPRIT RR160027 ) and by funding from the McNair Medical Institute at The Robert and Janice McNair Foundation. The Pacific Northwest National Laboratory (PNNL) proteomics work described herein was performed in the Environmental Molecular Sciences Laboratory, a US Department of Energy (DOE) National Scientific User Facility located at PNNL in Richland, Washington. PNNL is a multi-program national laboratory operated by the Battelle Memorial Institute for the DOE under contract DE-AC05-76RL01830 . Funding Information: This work was supported by the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) (U24CA159988, U24CA210954, U24CA160019, and U24CA210955) and the Cancer Prevention & Research Institutes of Texas (CPRIT RR160027) and by funding from the McNair Medical Institute at The Robert and Janice McNair Foundation. The Pacific Northwest National Laboratory (PNNL) proteomics work described herein was performed in the Environmental Molecular Sciences Laboratory, a US Department of Energy (DOE) National Scientific User Facility located at PNNL in Richland, Washington. PNNL is a multi-program national laboratory operated by the Battelle Memorial Institute for the DOE under contract DE-AC05-76RL01830. Conceptualization, H.R. R.D.S. K.D.R. D.C.L. T.L. and B.Z.; Methodology, S.V. C.H. X.W. V.A.P. S.R.S. B.W. Y.D. Y.Z. M.A.G. L.J.Z. D.C.L. T.L. and B.Z.; Software, S.V. C.H. X.W. V.A.P. S.S. B.W. Y.D. Y.Z. Z.S. O.A.A. J.E.M. M.E.M. M.C.C. Q.M. L.D. T.L. and B.Z.; Validation, S.V. C.H. X.W. V.A.P. S.R.S. B.W. Y.D. Y.Z. Z.S. O.A.A. L.J.Z. J.E.M. K.S.L. Q.M. M.E. K.D.R. D.C.L. T.L. and B.Z.; Formal Analysis, S.V. C.H. X.W. V.A.P. S.R.S. B.W. Y.D. Y.Z. Z.S. O.A.A. J.E.M. M.C.C. Q.M. L.D. T.L. and B.Z.; Investigation, M.A.G. L.J.Z. T.R.C. R.J.M. R.Z. M.E.M. Y.-T.W. R.J.C.S. D.C.L. and T.L.; Resources, R.D.S. K.D.R. D.C.L. T.L. and B.Z.; Data Curation, S.V. C.H. X.W. V.A.P. S.R.S. B.W. T.L. and B.Z.; Writing – Original Drafts, S.V. C.H. X.W. S.R.S. B.W. Y.D. Y.Z. M.T. T.L. and B.Z.; Write – Review & Editing, all authors; Visualization, S.V. C.H. X.W. S.R.S. B.W. Y.D. and Y.Z.; Supervision, R.D.S. K.D.R. D.C.L. T.L. and B.Z.; Project Administration, M.T. C.R.K. H.R. R.D.S. K.D.R. D.C.L. T.L. and B.Z.; Funding Acquisition, R.D.S. K.D.R. D.C.L. T.L. and B.Z. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = may,
day = "2",
doi = "10.1016/j.cell.2019.03.030",
language = "English (US)",
volume = "177",
pages = "1035--1049.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}