Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities.

Academic Article

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.
  • Authors

    Published In

  • Cell  Journal
  • Keywords

  • RB1, SOX9, biomarkers, colon cancer, drug targets, glycolysis, immune evasion, proteogenomics, proteomics, tumor antigen, Apoptosis, Biomarkers, Tumor, CD8-Positive T-Lymphocytes, Cell Proliferation, Colonic Neoplasms, Genomics, Glycolysis, Humans, Microsatellite Instability, Mutation, Phosphorylation, Prospective Studies, Proteogenomics, Proteomics, Retinoblastoma Protein
  • Digital Object Identifier (doi)

    Author List

  • Vasaikar S; Huang C; Wang X; Petyuk VA; Savage SR; Wen B; Dou Y; Zhang Y; Shi Z; Arshad OA
  • Start Page

  • 1035
  • End Page

  • 1049.e19
  • Volume

  • 177
  • Issue

  • 4