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.Liebler⁵¹⁵TaoLiu³¹⁵BingZhang^1271516

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 …