Decoy receptor 1 ( DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

摘要: Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate were selected from 389 involved Damage Repair by correlation analyses between gene methylation status drug response 32 cell lines. A large series samples (n=818) two phase III clinical trials was used evaluate these candidate correlating progression-free survival after first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) combination chemotherapy 5-fluorouracil plus (CAPIRI/FOLFIRI)). In the discovery (n=185) initial validation set (n=166), patients methylated Decoy Receptor 1 (DCR1) did not benefit CAPIRI over Capecitabine (discovery set: HR=1.2 (95%CI 0.7-1.9, p=0.6), HR=0.9 0.6-1.4, p=0.5)), whereas unmethylated DCR1 HR=0.4 0.3-0.6, p=0.00001), HR=0.5 0.3-0.7, p=0.0008)). These results could be replicated external data (n=467), where a similar effect size found FOLFIRI 5FU (methylated DCR1: HR=0.7 0.5-0.9, p=0.01), HR=0.8 0.6-1.2, p=0.4)). conclusion, promoter hypermethylation potential biomarker irinotecan, when combined capecitabine. This finding an set, which 5FU. underline challenge importance extensive evaluation multiple trials.