cfDNA methylation for screening and surveillance of colorectal cancer

Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarkers in many cancers. Here, we conducted a study to investigate the potential utility of ctDNA methylation markers in diagnosis and prognosis of colorectal cancer (CRC) and validate their effectiveness in early detection of asymptomatic CRC patients in a prospective cohort study. we compared methylation profiles of colorectal cancer (CRC) tissues and normal blood by analyzing 485,000 CpG markers and identified a CRC enriched methylation marker panel compared to that of normal blood. We then identified a CRC-specific methylation signature by comparing CRC tissues and normal blood leukocytes. After that, we applied machine learning to develop a predictive diagnostic and a prognostic model using ctDNA samples from a large cohort of CRC patients and normal controls. In addition, we generated a ctDNA based molecular subtype of CRC using an unsupervised clustering method. Finally, we validate the effectiveness of the diagnosis marker in more than 1000 persons with high risks for colorectal cancer in a prospective cohort study.