Proteomic signatures of colorectal cancer to identify distinct and reproducible subgroups independent of oncogenic mutations.

580 Background: While colorectal cancer (CRC) has classically been categorized on the basis of oncogenic mutations such as KRAS and BRAF, proteomic analyses directly elucidate the functional state of the cancer cell’s protein signaling, as recently described in a pan-cancer cohort and with mass-spectroscopy in a small CRC cohort. We performed an antibody-based proteomic analysis (reverse-phase protein array; RPPA) of a large cohort at MD Anderson (MDACC) and The Cancer Genome Atlas (TCGA) to determine patterns of protein expression in CRC. Methods: 725 archived CRC tumor samples (263 MDACC discovery set, and 462 TCGA validation set) underwent protein extraction and RPPA at MDACC to determine levels of 127 proteins. With unsupervised hierarchical clustering, samples dichotomized with distinct patterns of protein expression. The proteins with highest discriminatory utility were identified by LIMMA in the discovery set and confirmed in the validation set. Clinical variables and DNA sequencing results were av...