Abstract: Objective To investigate the clinical value of cg20657709 site methylation in the early detection of lung adenocarcinoma(LUAD). Methods The genome-wide DNA methylation profiling of peripheral blood mononuclear cells(PBMCs)and candidate differentially methylated position(DMP)were obtained from 30 LUAD patients and 45 healthy controls using Illumina Infinium MethylationEPIC BeadChip detection. Furthermore, the candidate DMP was validated in 35 LUAD patients and 30 healthy controls by pyrosequencing. Finally, multiple target region methylation enrichment sequencing was performed to evaluate the diagnostic value of DMP in the detection of lung adenocarcinoma in situ(AIS)in a cohort of 50 lung AIS patients and 50 healthy controls. Results Illumina Infinium MethylationEPIC BeadChip detection results showed that LUAD patients had specific genome-wide DNA methylation profiling based on PBMCs. The methylation levels of LUAD patients and healthy controls were significantly different. Initially, 1,345 DMPs were screened with the standard of∣Δβ∣≥0.06 and adjusted P<0.05. After multi-step screening, cg20657709 was determined as the candidate site. The cg20657709 site methylation was significantly higher in LUAD patients than in healthy controls (Δβ=0.097, adjusted P=0.004). Pyrosequencing results showed that cg20657709 site could clearly discriminate LUAD patients from healthy controls(AUC=0.946, sensitivity=91.4%, specificity=90.0%, cut-off value=66.91). Multiple target region methylation enrichment sequencing results showed cg20657709 site had good value in the detection of lung AIS(AUC=0.787, sensitivity=86.0%, specificity=64.0%, cut-off value=0.746 5). Conclusion Compared with healthy controls, LUAD patients have significantly higher cg20657709 site methylation, which is an important marker in the early detection of LUAD.

Key words: Lung adenocarcinoma, Peripheral blood mononuclear cell, Methylation, Early diagnosis, Clinical value