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PMID: 31010820 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing.

Clinical chemistry ·Vol. 65 ·No. 7 ·2019-00-00 ·Pages 916-926

Li J, Zhou X, Liu X, Ren J, Wang J, Wang W, Zheng Y, Shi X, Sun T, Li Z, Kang A, Tang F, Wen L, Fu W

Abstract

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. 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). Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) 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. MCTA-Seq is a promising method for the noninvasive detection of CRC.

MeSH Terms

Aged Algorithms Base Sequence Biomarkers, Tumor/blood,genetics Carcinoma, Hepatocellular/diagnosis Cell-Free Nucleic Acids/blood,genetics Colorectal Neoplasms/diagnosis CpG Islands DNA Methylation Diagnosis, Differential Female Humans Liver Neoplasms/diagnosis Male Middle Aged Nucleic Acid Amplification Techniques/methods Principal Component Analysis

Chemicals

Biomarkers, Tumor Cell-Free Nucleic Acids

Authors & Affiliations

14 authors, click to expand affiliations / ORCID

Li Jingyi

Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of General Surgery, Third Hospital, Peking University, Beijing, China. | Biomedical Pioneering Innovation Center, Peking University, Beijing, China. | National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Zhou Xin