DNA Methylation of LRRC3B: A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients.

BACKGROUND: Previous studies support a tumor-suppressor role for LRRC3B across various types of cancers. We aim to investigate the association between DNA methylation of LRRC3B and overall survival for early-stage non-small cell lung cancer patients.

METHODS: This study included 1,230 early-stage non-small cell lung cancer patients. DNA was extracted from lung tumor tissues and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. The association between DNA methylation and overall survival 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 overall survival was investigated in three independent groups of patients.

RESULTS: Three novel DNA methylation sites in LRRC3B were significantly associated with overall survival 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; P = 2.02×10-05) and validation cohort (HR = 0.55; P = 4.44×10-04). The three DNA methylation sites were significantly associated with LRRC3B expression, which was also associated with overall survival.

CONCLUSIONS: Using clinical data from a large population, we illustrated the association between DNA methylation of LRRC3B and overall survival of early-stage non-small cell lung cancer.

IMPACT: We provide evidence of plausibility for building biomarkers on DNA methylation of LRRC3B for overall survival of early-stage non-small cell lung cancer, thus filling a gap between previous in vitro studies and clinical applications.