Epigenome-Wide Association Analysis of Differentially Methylated Signals in Blood Samples of Patients with Non-Small-Cell Lung Cancer

Abstract

Lung cancer is a common form of cancer and the leading cause of cancer-related deaths worldwide. Early diagnosis using noninvasive biomarkers may play an important role in increasing the survival rate of patients with lung cancer. Biomarkers of DNA methylation in blood samples may improve the early diagnosis of lung cancer. Here, we used peripheral blood samples obtained from 150 patients diagnosed with non-small-cell lung cancer (NSCLC) and 150 healthy controls. The latter were selected by frequency matching with the 150 patients with NSCLC, based on age, sex, and smoking status. Genome-wide methylation profiles were obtained using a MethylationEPIC BeadChip Kit, which covers the 850k bp cytosine−phosphate−guanine site. This analysis showed two significant differentially methylated changes (cg12169243 [DPH6] and cg25429010 [IMP3]) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [USP7], cg06366994 [CPE], cg24992236 [MEG9], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [RSL24D1], cg04989085 [FAM113B], cg20905681 [CKAP4], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC. The validation of these DNA methylation changes and further research on the related genes may help develop easily accessible biomarkers for the early diagnosis or prognosis of NSCLC.

Keywords

• non-small-cell lung cancer
• DNA methylation
• biomarker