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

作者：Jingyi Li, Xin Zhou, Xiaomeng Liu, Jie Ren, Jilian Wang, Wendong Wang, Yuxuan Zheng, Xinyun Shi, Tao Sun, Zhifei Li, Anding Kang, Fuchou Tang, Lu Wen, Wei Fu · 发表于：Clinical Chemistry · 年份：2019 · DOI：10.1373/clinchem.2019.301804 · 被引用次数：41 · 研究领域：Cancer Genomics and Diagnostics、Epigenetics and DNA Methylation、Cancer Cells and Metastasis

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: ) 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.