A differentially-methylated-region signature predicts the recurrence risk for patients with early stage lung adenocarcinoma

Predicting prognosis in lung cancer patients is important in establishing future treatment and monitoring plans. Lung adenocarcinoma (LUAD) is the most common and aggressive type of lung cancer with dismal prognosis and prognostic stratification would help to guide treatment. Aberrant DNA methylation in tumors occurs earlier than clinical variations, and keeps accumulating as cancer progresses. Preliminary studies have given us some clues that DNA methylation might serve as a promising biomarker for prognosis prediction. Herein, we aimed to study the potential utility of DNA methylation pattern in predicting the recurrence risk of early stage resectable LUAD and to develop a risk-modeling signature based on differentially methylated regions (DMRs). This study consisted of three cohorts of 244 patients with stage I–IIIA LUAD, including marker discovery cohort (n = 39), prognostic model training cohort (n = 117) and validation cohort (n = 80). 468 DMRs between LUAD tumor and adjacent tissues were screened out in the marker discovery cohort (adjusted P < 0.05), and a prognostic signature was developed based on 15 DMRs significantly related to disease-free survival in early stage LUAD patients. The DMR signature showed commendable performance in predicting the recurrence risk of LUAD patients both in model training cohort (P < 0.001; HR = 4.32, 95% CI = 2.39–7.80) and model validation cohort (P = 0.009; HR = 9.08, 95% CI = 1.20–68.80), which might be of great utility both for understanding the molecular basis of LUAD relapse, providing risk stratification of patients, and establishing future monitoring plans.