Proteomic signatures of colorectal cancer to identify distinct and reproducible subgroups and to reflect prognosis.

3612 Background: While colorectal cancer (CRC) has classically been categorized by gene expression, proteomic analysis directly elucidates the functional state of protein signaling, which may better reflect cellular behavior. We performed an antibody-based proteomic analysis (reverse-phase protein array; RPPA) of a large cohort of MD Anderson (MDACC) and The Cancer Genome Atlas (TCGA) samples to determine patterns of protein expression in CRC. Methods: Protein was extracted from 725 archived CRC tumor samples (263 MDACC discovery set, and 462 TCGA validation set), and RPPA was performed to determine the expression levels of 127 cellular proteins. Upon 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 available for correlation. Results: Among the top 40 discriminant protei...