Abstract
We performed the first proteogenomic study on aprospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis ofpaired tumor and normal adjacent tissues produceda 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 colontumors and suggests a rationalefor targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 Tcell 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 checkpointblockade. Proteogenomics presents new avenuesfor biological discoveries and therapeutic development.
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