Liquid biopsy in human non-small-cell lung cancer. Blood-based analysis of ctDNA methylation

BackgroundUse of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs).ObjectivesSystematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without amalign disease.MethodsQuantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing.ResultscfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed asensitivity of 52% in NSCLC patients and aspecificity of 90% in the post-NSCLC group (AUC: 0.69; p<0.05).ConclusionsPromotor hypermethylation of the potential biomarker CFTR shows adiscriminatory potential for differentiation of NSCLC patients to patients without amalign disease and should further be investigated.