Peripheral blood-based hypomethylation as a biomarker for the early-stage non-small cell lung cancer.

[AIM] Non-small cell lung cancer (NSCLC) has caused a heavy social and economic burden worldwide. DNA methylation, as an emerging blood biomarker, has great potential for early detection of NSCLC.

[METHODS] Seven CpG sites of the gene were detected quantitatively using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry in 845 NSCLC patients (91.4% at stage I) and 1007 controls. Logistic regression was used to calculate covariate-adjusted ORs and 95% CIs.

[RESULTS] The logistic regression-based quartile analysis (Q1 lowest vs. Q4 highest) disclosed the association between hypomethylation of six CpG sites in the gene and NSCLC (ORs ranged from 1.51 to 2.32, and for trend ≤0.004 for all), and even in NSCLC at stage I (ORs ranged from 1.53 to 2.26, and for trend ≤0.004 for all). The subgroup analyses suggested enhanced association in male gender and older age. Additionally, decreased methylation of S100P_CpG_5 was markedly relevant with advanced tumor size and tumor stage ( = 0.003 and  = 0.007, respectively).

[CONCLUSIONS] Using quantitative mass spectrometry, we investigated an association between hypomethylation in peripheral blood and NSCLC and suggested the great potential of DNA methylation signatures in whole blood for early detection of NSCLC.