Open AccessMethylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma
Author(s) -
Tao Fu,
Anup Sharmab,
Fei Xie,
Yanliang Liu,
Kai Li,
Weiwei Wan,
Stephen B. Baylin,
Christopher L. Wolfgang,
Nita Ahuja
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0162929
Subject(s) - microsatellite instability , o 6 methylguanine dna methyltransferase , methyltransferase , methylation , oncology , kras , medicine , dna methylation , adenocarcinoma , hazard ratio , univariate analysis , proportional hazards model , survival analysis , stage (stratigraphy) , lymphovascular invasion , cancer research , biology , cancer , multivariate analysis , colorectal cancer , genetics , metastasis , allele , gene , confidence interval , paleontology , gene expression , microsatellite
Background O 6 -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.