Diagnostic and Prognostic Characteristics of Circulating Free DNA Methylation Detected by the Electrochemical Method in Malignant Tumors

Simple SummaryPrevious studies have established an electrochemical detection method for the rapid detection of cfDNA (circulating free DNA) methylation and found that this technology might be a potential method for cancer diagnosis. However, the underlying mechanism and its role in the diagnosis and prognosis of malignant tumors are not well-characterized. In present study, we utilized the electrochemical detection method to detect the DNA methylation status by using electron microscopies and infrared spectroscopy and found that DNA with different methylated levels adsorbed to the gold surface differently, which was likely mediated by hydrophobic bonds. In addition, after detection of the cfDNA methylation status from 505 normal individuals, 725 cancer patients before treatment, and 549 patients after treatment, we found that the cfDNA adsorption rate could be used as an indicator for the diagnosis and prognosis prediction of pan-cancer. Our research provides a novel method for the liquid biopsy of cancer for diagnosis and prognosis predictions.AbstractPrior research has established an electrochemical method based on the differential adsorption capacity of gold surfaces with different methylated DNA degrees and found that this method might be valuable for cancer diagnosis by detecting circulating free DNA methylation. However, further investigation on the underlying mechanism and validation of its diagnostic and prognostic values in a large cohort of malignant tumors was limited. We found that DNA with different methylation levels formed particles of diverse sizes on the gold surface. Hydrophobic bonds played a significant role in the binding process of methylated DNA to the gold surface. The detection condition of an adsorption time of 10 min and temperature of 20 °C was optimal. In a large cohort of plasma samples from the patients with different malignant tumors, as well as normal individuals, we found that the electrochemical detection method based on the differential adsorption capacity of methylated DNA degree on a gold surface could be used as a noninvasive tool for malignant tumor diagnosis and prognostic evaluation. The diagnostic efficiency of this method in malignant tumors was even slightly better than that of the current tumor biomarkers widely used in routine clinical practice (circulating free DNA (cfDNA) vs. carcinoembryonic antigen (CEA), 0.8131 vs. 0.7191 and cfDNA vs. CA19-9, 0.7687 vs. 0.6693).Keywords:electrochemical;circulating free DNA methylation;malignant tumor;diagnostic;prognostic