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.