Evaluation of Methylated DCR1 As a Biomarker for Response to Adjuvant Irinotecan-based Therapy in Stage III Colon Cancer: Cancer and Leukaemia Group B 89803 (Alliance)

Overview

Journal Epigenetics

Specialty Genetics

Date 2022 Apr 12

PMID 35412430

Authors

Lynn Symonds

Ming Yu

YuHong Zhang

Fang-Shu Ou

Tyler J Zemla

Kelly Carter

Monica Bertagnolli

Federico Innocenti

Linda Jw Bosch

Gerrit A Meijer

Beatriz Carvalho

William M Grady

Stacey A Cohen

Affiliations

Soon will be listed here.

Abstract

Aberrantly methylated genes contribute to the landscape of epigenetic alterations in colorectal adenocarcinoma. The global CpG Island methylator phenotype (CIMP) and individually methylated genes are potential prognostic/predictive biomarkers. Research suggests an association between methylated (m) and lack of benefit with irinotecan (IFL) treatment. We assessed the association between methylation status and survival in patients receiving adjuvant fluorouracil/ leucovorin (5-FU/LV) or IFL. We analysed data from patients with stage III colon adenocarcinoma randomly assigned to adjuvant 5-FU/LV or IFL in CALGB 89803 (Alliance). The primary endpoint was overall survival (OS), and the secondary endpoint was disease-free survival (DFS). Using tumour sample DNA, we evaluated the association between survival, methylation status, and molecular subgroups (, mismatch repair status, CIMP status) using Kaplan-Meier estimator and Cox proportional hazard model. m was observed in 221/400 (55%) colon cancers. Histopathologic features were similar between m and unmethylated (un) colon cancers. There was no difference in OS ( = 0.83) or DFS ( = 0.85) based on methylation status. There was no association between methylation status and response to IFL . In patients with un and -wildtype tumours, those who received IFL had a nearly two-fold worse DFS compared to patients who received 5-FU/LV (HR = 1.85, 95% CI (0.97-3.53, = 0.06). This relationship was not notable among other subgroups. In stage III colon cancer patients, m status did not associate with response to irinotecan. Larger studies may suggest an association between the iridocene response and molecular subgroups.

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