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The clinicopathological significance of hMLH1 hypermethylation in non-small-cell lung cancer: a meta-analysis and literature review

Authors Han Y, Shi K, Zhou S, Yu D, Liu Z

Received 13 February 2016

Accepted for publication 7 May 2016

Published 16 August 2016 Volume 2016:9 Pages 5081—5090

DOI https://doi.org/10.2147/OTT.S106345

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 5

Editor who approved publication: Professor Min Li


Yi Han, Kang Shi, Shi-Jie Zhou, Da-Ping Yu, Zhi-Dong Liu

Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China

Abstract: The hMLH1 gene plays an essential role in DNA repair. Methylation of the hMLH1 gene is common in many types of cancer and can lead to the loss of hMLH1 expression. However, the association and clinicopathological significance between hMLH1 promoter hypermethylation and non-small-cell lung cancer (NSCLC) is elusive. Here, we investigated the correlation of hMLH1 promoter hypermethylation and NSCLC using 13 studies by comprising 1,056 lung cancer patients via a meta-analysis. We observed that 1) loss of hMLH1 protein expression was significantly associated with its promoter hypermethylation, 2) hMLH1 gene inactivation through hypermethylation contributed to the tumorigenesis of NSCLC, which could be a decisive factor for the pathogenesis of NSCLC due to its high occurrence in NSCLC tissues compared to normal lung tissues, 3) a correlation exists between histologic subtypes/disease stages (TNM I+II vs III+IV) and hypermethylation status of hMLH1 gene, and 4) NSCLC patients with hMLH1 hypermethylation and subsequent low expression levels of hMLH1 have a short overall survival period than those patients with normal expression of hMLH1 gene. hMLH1 mRNA predicts patient survival in lung cancer, and this was confirmed by using a public database. We then discussed the tumor suppressor function of hMLH1 and the clinicopathological significance of hMLH1 in NSCLC. We concluded that hMLH1 hypermethylation should be an early diagnostic marker for NSCLC and also a prognostic index for NSCLC. hMLH1 is an interesting therapeutic target in human lung cancers.

Keywords: non-small-cell lung cancer, NSCLC, hMLH1 gene, methylation, meta-analysis

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