Prediction of disease-free survival of N1/2 non-small cell lung cancer after adjuvant chemotherapy by the biomarker RPMB

Abstract

No molecular biomarkers have been proven applicable in clinical practice to identify patients who can benefit from adjuvant chemotherapy in non-small cell lung cancer (NSCLC). In this study, we established a biomarker, RPMB, short for promotor methylation burden of DNA repair genes (DRGs), to identify the subgroup of patients who might benefit from adjuvant chemotherapy in NSCLC. Methylation profiles of 828 NSCLC primary tumors and their clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The RPMB for each patient after radical resection was calculated and its correlation with the prognosis of NSCLC was extensively investigated. DRGs of NSCLC were much more hypomethylated than the other genes (all p＜0.001). RPMB was defined as the ratio of methylated DRGs to the total number of all the DRGs. Patients with higher RPMB values tended to be nonsmokers, had adenocarcinoma, were female and had peripheral tumors. Subgroup analysis of forest plot among different clinical factors showed that high RPMB was significantly correlated to better disease-free survival (DFS) in pathologic N-positive patients after adjuvant chemotherapy (HR = 0.404, n = 62, p = 0.034). Notably, more superior DFS was exhibited in high RPMB NSCLCs with N1 nodal stage compared with those with low RPMB values (HR = 0.348, n = 47, p = 0.043). High RPMB might be used as a potential predictor to identify suitable N-positive NSCLC patients who can benefit from adjuvant chemotherapy after radical surgery.