RNA sequencing profiles and diagnostic signatures linked with response to ramucirumab in gastric cancer
Published on Feb 14, 2020
· DOI :10.1101/MCS.A004945
Gastric cancer (GC) is the fifth cancer type by associated mortality. Proportion of early diagnosis is low, and most patients are diagnosed at the advanced stages. First line therapy standardly includes fluoropyrimidines and platinum compounds with trastuzumab for HER2-positive cases. For the recurrent disease there are several alternative options including ramucirumab, a monoclonal therapeutic antibody that inhibits VEGF-mediated tumor angiogenesis by binding with VEGFR2, alone or in combination with other cancer drugs. However, control over disease rate following ramucirumab or its combinations is 30-80% of the patients, suggesting that personalization of drug prescription is needed to increase efficacy of treatment. We report here original tumor RNA sequencing profiles for 15 advanced GC patients linked with data on clinical response to ramucirumab or its combinations. Three genes showed differential expression in the tumors-responders vs non-responders: CHRM3, LRFN1 and TEX15. Of them, CHRM3 was upregulated in the responders. Using bioinformatic platform Oncobox we simulated ramucirumab efficiency and compared output model results with actual tumor response data. An agreement was observed between predicted and real clinical outcomes (AUC >/= 0.7). These results suggest that RNA sequencing may be used to personalize prescription of ramucirumab for GC and indicate on potential molecular mechanisms underlying ramucirumab resistance. The RNA sequencing profiles obtained here are fully compatible with the previously published Oncobox Atlas of Normal Tissue Expression (ANTE) data.