Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities


主讲人:窦永超 贝勒医学院




内容介绍: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.