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

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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 MLH1 MSP 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.

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