Proteogenomic Landscape of Gastric Adenocarcinoma Peritoneal Metastases

Abstract Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcomes. Therapeutic are limited and effective. Here we report the first proteogenomic study of PC cells from a prospective GAC cohort (n = 26 patients). A total of 16,449 proteins were detected from whole cell extracts (TCEs). PC cells could be classified based on the protein profiles alone into three distinct unsupervised clusters (tumor cell enriched, immune cell enriched and tumor-immune mixed) that differed in expression of oncogene/immune-related proteins. Integrated analysis revealed enriched biological pathways and notably, novel druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression levels of proteins and mRNAs revealed novel expression patterns of key cancer genes notably high mRNA and low protein expression of HAVCR2, low mRNA but high protein expression of cancer testis antigens CTAGE1 and CTNNA2. These results inform strategies to target GAC vulnerabilities.