Cell: Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities
Author links open overlay panelSuhasVasaikar1214ChenHuang1214XiaojingWang121214Vladislav A.Petyuk314Sara R.Savage414BoWen12YongchaoDou12YunZhang1ZhiaoShi12Osama A.Arshad3Marina A.Gritsenko3Lisa J.Zimmerman5Jason E.McDermott3Therese R.Clauss3Ronald J.Moore3RuiZhao3Matthew E.Monroe3Yi-TingWang3Matthew C.Chambers5Robbert J.C.Slebos5Ken S.Lau6QianxingMo713LiDing8MatthewEllis17MathangiThiagarajan9Christopher R.Kinsinger10HenryRodriguez10Richard D.Smith3Karin D.Rodland31115Daniel C.Liebler515TaoLiu315BingZhang1271516
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 …
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