Clin Chem 2019 Jul 22;65(7):916-926. Epub 2019 Apr 22.
Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of General Surgery, Third Hospital, Peking University, Beijing, China;
Background: Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types.
Methods: We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36).
Results: Dozens of DNA hypermethylation markers including known (e.g., and ) and novel (e.g., , , , , and ) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers.
Conclusions: MCTA-Seq is a promising method for the noninvasive detection of CRC.