Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma

PLoS One. 2016 Sep 19;11(9):e0162929. doi: 10.1371/journal.pone.0162929. eCollection 2016.

Abstract

Background: O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA.

Methods: Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations.

Results: MGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups.

Conclusions: Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / therapeutic use
  • Chemoradiotherapy
  • DNA Methylation*
  • Duodenal Neoplasms / enzymology
  • Duodenal Neoplasms / pathology*
  • Duodenal Neoplasms / therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • Prognosis

Substances

  • Antineoplastic Agents
  • O(6)-Methylguanine-DNA Methyltransferase

Grant support

This work was supported by National Institutes of Health grants CA140599 and CA127141, National Natural Science Foundation of China grants 81000898 and 81472289, and sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China.