Cell-free Methylated Plasma DNA As a Biomarker for Therapy Monitoring in Advanced Stage NSCLC and SCLC Patients

Still most lung cancer patients present with a late-stage disease at the time of diagnosis. This holds true for NSCLC and SCLC patients alike. The recently developed approach for the analysis of cell-free nucleic acids, i.e. liquid profiling, has gained more acceptance especially in follow-up and therapy monitoring studies. We aimed to find out whether the quantification of cell-free circulating methylated plasma DNA is a useful method for the therapy monitoring of patients treated with different therapy regimens. In our study we analyzed 96 NSCLC and 42 SCLC patients. Blood samples were obtained before start of therapy and during the therapy until the point of first re-staging. The cell-free plasma DNA was quantified for the amount of methylated SHOX2 and PTGER4 genes. While for NSCLC patients the baseline values for mPTGER4 and mSHOX2 did not allow for clear discrimination between different response groups, the combination of the methylation values for both genes showed a clear difference between responders vs. non-responders at the time of re-staging. For SCLC patients the baseline values of mPTGER4 and mSHOX2 did not show a statistical significant difference between response groups but at time of re-staging, both markers were considerably lower in patients with partial remission as compared with patients demonstrating a stable and progressive disease. These findings demonstrate that the quantification of free-circulating methylated plasma DNA could be a valuable tool to monitor the response of late stage NSCLC and SCLC patients undergoing systemic treatment regimens.