Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: a multicentre cohort study

作者：Shaobo Mo, Weixing Dai, Hui Wang, Xiao-Liang Lan, Chengcheng Ma, Zhixi Su, Wenqiang Xiang, Lingyu Han, Wenqin Luo, Long Zhang, Renjie Wang, Yaodong Zhang, Wenming Zhang, Lin Yang, Renquan Lu, Lin Guo, Ying Zheng, Mingzhu Huang, Ye Xu, Liang Li, Sanjun Cai, Guo‐Xiang Cai · 发表于：EClinicalMedicine · 年份：2022 · DOI：10.1016/j.eclinm.2022.101717 · 被引用次数：86 · 研究领域：Cancer Genomics and Diagnostics、Genetic factors in colorectal cancer、Colorectal Cancer Screening and Detection

Background: Early detection and prognosis prediction of colorectal cancer (CRC) can significantly reduce CRC-related mortality. Recently, circulating tumour DNA (ctDNA) methylation has shown good application foreground in the early detection and prognosis prediction of multiple tumours. Methods: This multicentre cohort study evaluated ctDNA methylation haplotype patterns based on archived plasma samples (collected between 2010 and 2018) from 1138 individuals at two medical centres: Fudan University Shanghai Cancer Center (Shanghai, China) and Southern Medical University Nanfang Hospital (Guangzhou, Guangdong, China), including 366 healthy individuals, 182 patients with advanced adenoma (AA), and 590 patients with CRC. Samples were processed using the ColonES assay, a targeted bisulfite sequencing method that detects ctDNA methylation haplotype patterns in 191 genomic regions. Among these 1138 samples, 748 were used to develop a classification model, and 390 served as a blinded cohort for independent validation. The study is registered at https://register.clinicaltrials.gov with the unique identifier NCT03737591. Results: The model obtained from unblinded samples discriminated patients with CRC or AA from normal controls with high accuracy. In the blinded validation set, the ColonES assay achieved sensitivity values of 79.0% (95% confidence interval (CI), 66%-88%) in AA patients and 86.6% (95% CI, 81%-91%) in CRC patients with a specificity of 88.1% (95% CI, 81%-93%) in health...