Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers.
Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I-III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.
['Cho|Nam-Yun|NY|0000-0002-2126-9549', 'Park|Ji-Won|JW|0000-0003-0046-8175', 'Wen|Xianyu|X|0000-0003-1523-0776', 'Shin|Yun-Joo|YJ|', 'Kang|Jun-Kyu|JK|', 'Song|Sang-Hyun|SH|', 'Kim|Hwang-Phill|HP|', 'Kim|Tae-You|TY|', 'Bae|Jeong Mo|JM|', 'Kang|Gyeong Hoon|GH|0000-0003-2380-6675']
colorectal cancer methylation cfDNA MethyLight droplet digital PCR plasma