DNA methylation signature predictive of benefit from neoadjuvant chemotherapy in esophageal adenocarcinoma: Results from the MRC OEO2 phase III trial.

43Background: Platinum and 5-Fluorouracil (5FU) neoadjuvant chemotherapy followed by surgery is one of the standard approaches for patients with resectable EAC. To date, there are no predictive biomarkers of chemotherapy benefit. We hypothesize that DNA methylation of genes in key biologic and oncogenic pathways predict for chemotherapy benefit in EAC. Methods: In the OE02 trial, 802 patients with resectable esophageal carcinoma were randomised to surgery alone (S) versus two cycles of cisplatin and 5FU chemotherapy followed by surgery (CS). DNA was extracted from 213 EAC resection specimens (110 from the (CS) arm, 103 from the (S) arm). DNA methylation was analyzed at 1505 CpG sites within 807 genes using the Illumina GoldenGate platform. Cox proportional hazard analysis was performed to identify predictive markers of survival in (CS) arm; non-negative matrix factorization (NMF) was used to delineate methylation signatures. Results: Methylation status of 1505 CpG sites had no statistical difference betwe...