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Role of MLH1 methylation in esophageal cancer carcinogenesis and its clinical significance

Authors Li J, Ye D, Wang L, Peng Y, Li Q, Deng H, Zhou C

Received 24 October 2017

Accepted for publication 15 November 2017

Published 1 February 2018 Volume 2018:11 Pages 651—663

DOI https://doi.org/10.2147/OTT.S154999

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Jinyun Li,1 Dong Ye,2 Lei Wang,3 Yingying Peng,3 Qun Li,2 Hongxia Deng,2 Chongchang Zhou2

1Department of Oncology and Hematology, Affiliated Hospital of Ningbo University, 2Department of Otorhinolaryngology – Head and Neck Surgery, 3Department of General Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China

Abstract: The mutL homolog-1 (MLH1) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20–2.66), advanced tumor grade (OR=3.7; 95% CI =2.37–5.77), lymph node metastasis (OR=2.65; 95% CI =1.81–3.88), distant metastasis (OR=7.60; 95% CI =1.23–47.19), advanced clinical stage (OR=4.46; 95% CI =2.88–6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00–2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC.

Keywords: MLH1, methylation, esophageal cancer, carcinogenesis, diagnosis, prognosis

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