MutL同源蛋白1的异常甲基化与非小细胞肺癌风险增加相关。

Aberrant methylation of mutL homolog 1 is associated with increased risk of non-small cell lung cancer.

作者信息

Hu Haochang, Chen Xiaoying, Zhou Cong, Li Bin, Yang Yong, Ying Xiuru, Mao Yiyi, Zhang Yihan, Zhong Jie, Dai Jie, Yu Hang, Wu Boyi, Li Xiaodong, Wang Tiangong, Duan Shiwei

机构信息

Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.

Department of Medical Record, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

J Clin Lab Anal. 2018 Jun;32(5):e22370. doi: 10.1002/jcla.22370. Epub 2017 Dec 5.

DOI:10.1002/jcla.22370

PMID:29205508

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6816959/

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is a common malignant tumor. DNA hypermethylation in the promoter region has been served as a potential molecular marker for several tumors. The goal of the current study was to assess the diagnostic ability of mutL homolog 1 (MLH1) promoter methylation in NSCLC.

METHODS

A total of 111 NSCLC patients' paired tissue samples were obtained to explore the association between MLH1 promoter methylation and NSCLC by methylation-specific polymerase chain reaction (MSP) method. Public databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to verify our findings.

RESULTS

Our results showed a significantly higher MLH1 methylation frequency in tumor tissue samples than their paired adjacent tissues (P = .008). ROC curve indicated that MLH1MSP assay was a sensitive but not a specific method in the diagnosis for NSCLC (sensitivity = 0.964, specificity = 0.135, AUC = 0.550). And the association between the methylation level and clinical characteristics has no statistical significance. TCGA cohort evinced a higher methylation probability in tumor group compared with nontumor group (the mean β value: -0.449 [-0.467, -0.437] vs -0.466 [-0.472, -0.437], P = .011), which was consistent with our results. Meanwhile, an inverse correlation between MLH1 methylation and MLH1 expression was detected in TCGA and GEO databases.

CONCLUSIONS

The MSP method for MLH1 methylation was a sensitive but not a specific diagnostic method for NSCLC.

摘要

背景

非小细胞肺癌（NSCLC）是一种常见的恶性肿瘤。启动子区域的DNA高甲基化已被用作多种肿瘤的潜在分子标志物。本研究的目的是评估错配修复蛋白同源物1（MLH1）启动子甲基化在NSCLC中的诊断能力。

方法

通过甲基化特异性聚合酶链反应（MSP）方法，共获取111例NSCLC患者的配对组织样本，以探讨MLH1启动子甲基化与NSCLC之间的关联。使用包括癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）在内的公共数据库来验证我们的研究结果。

结果

我们的结果显示，肿瘤组织样本中MLH1甲基化频率显著高于其配对的癌旁组织（P = 0.008）。ROC曲线表明，MLH1 MSP检测在NSCLC诊断中是一种敏感但非特异性的方法（敏感性 = 0.964，特异性 = 0.135，AUC = 0.550）。并且甲基化水平与临床特征之间的关联无统计学意义。TCGA队列显示，肿瘤组的甲基化概率高于非肿瘤组（平均β值：-0.449 [-0.467, -0.437] 对 -0.466 [-0.472, -0.437]，P = 0.011），这与我们的结果一致。同时，在TCGA和GEO数据库中检测到MLH1甲基化与MLH1表达呈负相关。