DNA methylation and expression of MAPRE3 affect overall survival of early‐stage non‐small cell lung cancer patients

The MAPRE3 gene is aberrantly expressed in several cancers. We profiled DNA methylation in tumor tissues from early‐stage non‐small cell lung cancer (NSCLC) patients and assessed associations with overall survival (OS). Significant CpG probes were validated in The Cancer Genome Atlas (TCGA). The methylation level of cg12821679 MAPRE3 showed significant associations with OS in lung squamous cell carcinoma (LUSC) (HR = 0.32, P = 6.55 × 10 −7 ), but it was not observed in lung adenocarcinoma (LUAD). In LUSC, MAPRE3 expression was significantly correlated with cg12821679 MAPRE3 ( r = 0.17, P = 2.96 × 10 −3 ) and potential trans ‐regulated genes were enriched in the Nicotine addiction pathway. Additionally, MAPRE3 expression showed significant associations with OS in both LUAD and LUSC (LUAD: HR low vs high = 2.28, P = 2.40 × 10 −3 ; LUSC: HR low vs high = 1.61, P = 0.0244). The association between smoking cessation and overall survival was significantly modified by MAPRE3 expression (HR interaction = 0.69, P = 0.0282). Smoking cessation improved OS only in patients with high MAPRE3 expression (HR = 0.56, P = 2.82 × 10 −3 ). We conclude MAPRE3 may predict NSCLC prognosis and influence the prognostic benefit of smoking cessation.