Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer.

摘要: Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients evaluate their potential suitability alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved 5-fluoruracil (5-FU) metabolism as well platinum resistance, previously identified genomic subtypes predicting 5-FU benefit, mRNA expression levels receptor tyrosine kinases KRAS treatment targets a single institution cohort 252 GC treated with without after D2 gastrectomy. Results: 88% 62% had sensitive phenotype by SNP analyses TS 3'UTR, 5'UTR, respectively. 24%, 46%, 40%, 5%, 44% GSTP1, ERCC1 rs11615, rs3212986, ERCC2, XRCC1, High HER2, EGFR, FGFR2, MET observed 49%, 66%, 72%, 54% GC, HER2 the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). (p=0.031), low EGFR (p=0.124), high (p=0.165) RNA expression, 5'UTR subtype 2R/2R, 2R/3C, 3C (p=0.058) were independent predictors resistance. Conclusions: The present study suggests that platinum-based RTK agents could be options substantial subgroup currently S-1. MET, appear promising resistance warranting validation an series.