GNPS - Integrative proteogenomic characterization of colorectal cancer cell lines and primary tumors

Solid tumors are complex organs comprising neoplastic cells and stroma, yet cancer cell lines remain widely used to study tumor biology, biomarkers and experimental therapy. Here, we performed a fully integrative analysis of global proteomic data comparing human colorectal cancer (CRC) cell lines to primary tumors and normal tissues. We found a significant, systematic difference between cell line and tumor proteomes, with a major contribution from tumor stroma proteomes. Nevertheless, cell lines overall mirrored the proteomic differences observed between tumors and normal tissues, in particular for genetic information processing and metabolic pathways, indicating that cell lines provide a system for the study of the intrinsic molecular programs in cancer cells. Intersection of cell line data with tumor data provided insights into tumor cell specific proteome alterations driven by genomic alterations. Our integration of cell line proteogenomic data with drug sensitivity data highlights the potential of proteomic data in predicting therapeutic response. We identified representative cell lines for the proteomic subtypes of primary tumors, and linked these to drug sensitivity data to identify subtype-specific drug candidates.