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

Abstract:

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., 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. CONCLUSIONS:MCTA-Seq is a promising method for the noninvasive detection of CRC.

journal_name

Clin Chem

journal_title

Clinical chemistry

authors

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

doi

10.1373/clinchem.2019.301804

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

916-926

issue

7

eissn

0009-9147

issn

1530-8561

pii

clinchem.2019.301804

journal_volume

65

pub_type

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