Aberrant Methylation of SLIT2 Gene in Plasma Cell-Free DNA of Non-Small Cell Lung Cancer Patients

This study aimed to understand aberrant methylation of genes as a biomarker for the early detection and prognosis prediction of non-small cell lung cancer (NSCLC). Methylation levels of were determined using the Infinium HumanMethylation450 BeadChip or pyrosequencing. Five CpGs at the CpG island of , or genes were significantly (Bonferroni corrected < 0.05) hypermethylated in tumor tissues obtained from 42 NSCLC patients than in matched normal tissues. Methylation levels of these CpGs did not differ significantly between bronchial washings obtained from 76 NSCLC patients and 60 cancer-free patients. However, methylation levels of gene were significantly higher in plasma cell-free DNA of 72 NSCLC patients than in that of 61 cancer-free patients ( = 0.001, Wilcoxon rank sum test). Prediction of NSCLC using methylation was achieved with a sensitivity of 73.7% and a specificity of 61.9% in a plasma test dataset ( = 40). A Cox proportional hazards model showed that hypermethylation in plasma cell-free DNA was significantly associated with poor recurrence-free survival (hazards ratio = 2.19, 95% confidence interval = 1.21-4.36, = 0.01). The present study suggests that aberrant methylation of in plasma cell-free DNA is a valuable biomarker for the early detection of NSCLC and prediction of recurrence-free survival. However, further research is needed with larger sample size to confirm results.