The association between blood-based HYAL2 methylation and early-stage lung cancer: a case-control study.

Abstract

Background: Blood-based DNA methylation biomarkers have great potential for the early detection of lung cancer (LC). Here, we investigated the association between HYAL2 methylation in peripheral blood and LC.

Methods: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed to measure the methylation levels of 4 CpG sites in HYAL2 gene in two independent case-control studies (168 LC cases and 167 controls in Study I, 677 LC cases and 833 controls in Study II). Logistic regression adjusted for covariates was conducted for odds ratios (ORs) and 95% confidence intervals (CIs). Non-parametric tests were applied for the comparisons of stratified groups.

Results: Hypomethylation of all 4 CpG sites in HYAL2 was associated with early-stage LC in the two studies (ORs range from 1.91 to 3.07 in Study I, ORs range from 1.39 to 1.86 in Study II, p < 0.05 for all). The associations were still significant for the very early-stage LC patients (stage I). Subgroup analysis indicated that the associations could be enhanced by male gender and older age. Moreover, decreased HYAL2 methylation was correlated with increased tumor size, tumor length and stage.

Conclusions: Our results suggested blood-based HYAL2 hypomethylation as a potential biomarker for LC early detection.