DNA Methylation of : A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients.

BACKGROUND

Previous studies support a tumor-suppressor role for across various types of cancers. We aimed to investigate the association between DNA methylation of and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC).

METHODS

This study included 1,230 patients with early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. The association between DNA methylation and OS was first tested using Cox regression on a discovery cohort and then validated in an independent cohort. Next, the association between DNA methylation and gene expression was investigated in two independent cohorts. Finally, the association between gene expression and OS was investigated in three independent groups of patients.

RESULTS

Three novel DNA methylation sites in were significantly associated with OS in two groups of patients. Patients with hypermethylation in the DNA methylation sites had significantly longer survival than the others in both the discovery cohort (HR, 0.62; = 2.02 × 10) and validation cohort (HR, 0.55; = 4.44 × 10). The three DNA methylation sites were significantly associated with expression, which was also associated with OS.

CONCLUSIONS

Using clinical data from a large population, we illustrated the association between DNA methylation of and OS of early-stage NSCLC.

IMPACT

We provide evidence of plausibility for building biomarkers on DNA methylation of for OS of early-stage NSCLC, thus filling a gap between previous studies and clinical applications.