Genome-wide cell-free DNA methylation profiling in advanced stage ovarian cancer. Are we looking at the tumor or the patient's immune response to the tumor?

Résumé fourni par la source

• MeD-seq provides a reliable method for genome wide methylation profiling of cfDNA • Ovarian cancer patients showed a distinct cfDNA methylation signature • Preoperative hypermethylation scores were significantly higher than postoperative hypermethylation scores • The cfDNA methylation signature differed from tumor tissue of the same patient • The cfDNA methylation signature was more related to immune-related cells The aim of this study was to identify differentially methylated regions in cell-free DNA (cfDNA) between healthy persons and patients with advanced stage ovarian cancer (ASOC) and to identify differences in cfDNA methylation before and after cytoreductive surgery. Plasma-derived cfDNA was analyzed by a high-throughput genome wide DNA methylation sequencing technique: MeD-seq. A training set of therapy naïve cfDNA samples of patients with ASOC (≥FIGO stage IIIB, n=10) was compared with cfDNA of healthy controls (n=10) to define a ASOC specific cfDNA methylation signature. A cumulative hypermethylation score was constructed and a validation set of pre- and postoperative samples of 39 patients were compared using this score. MeD-seq results of tumor tissue samples were correlated with cfDNA results. Patients with ASOC showed a clear distinct cfDNA methylation signature from healthy controls (p<0.0001). This cfDNA-methylation signature resulted in preoperative hypermethylation scores (135; interquartile range 110–163) that were significantly higher than postoperative hypermethylation scores (91; interquartile range 76–101) (p<0.001). The cfDNA methylation signature at baseline differed from tumor tissue and was more closely related to DNA methylation of immune-related cells (T-lymphocytes, neutrophil granulocytes, monocytes, and B-lymphocytes) than to ASOC tissue. MeD-seq provides a promising method for genome wide methylation profiling of cfDNA. Patients with ASOC could clearly be distinguished from healthy controls and differed pre- and postoperatively.

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