Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study

作者：De‐Zhen Guo, Ao Huang, Ying‐Chao Wang, Shuang Zhou, Hui Wang, Xianglei Xing, Shi‐Yu Zhang, Jianwen Cheng, Ke‐Hui Xie, Qichang Yang, Chengcheng Ma, Qing Li, Yan Chen, Zhixi Su, Jia Fan, Rui Liu, Xiaolong Liu, Jian Zhou, Xin‐Rong Yang · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1652 · 被引用次数：37 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Genomics and Diagnostics、Epigenetics and DNA Methylation

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124...