Identification of DNA methylation signatures for hepatocellular carcinoma detection and microvascular invasion prediction

作者：Yijie Hao, Qingxia Yang, Qiye He, Huanjing Hu, Zongpeng Weng, Zhixi Su, Shuling Chen, Sui Peng, Ming Kuang, Zhihang Chen, Lixia Xu · 发表于：European journal of medical research · 年份：2022 · DOI：10.1186/s40001-022-00910-w · 被引用次数：19 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Colorectal Cancer Surgical Treatments、Cancer Genomics and Diagnostics

BACKGROUND AND AIM: Preoperative evaluation of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) is important for surgical strategy determination. We aimed to develop and establish a preoperative predictive model for MVI status based on DNA methylation markers. METHODS: A total of 35 HCC tissues and the matched peritumoral normal liver tissues as well as 35 corresponding HCC patients' plasma samples and 24 healthy plasma samples were used for genome-wide methylation sequencing and subsequent methylation haplotype block (MHB) analysis. Predictive models were constructed based on selected MHB markers and 3-cross validation was used. RESULTS: We grouped 35 HCC patients into 2 categories, including the MVI- group with 17 tissue and plasma samples, and MVI + group with 18 tissue and plasma samples. We identified a tissue DNA methylation signature with an AUC of 98.0% and a circulating free DNA (cfDNA) methylation signature with an AUC of 96.0% for HCC detection. Furthermore, we established a tissue DNA methylation signature for MVI status prediction, and achieved an AUC of 85.9%. Based on the MVI status predicted by the DNA methylation signature, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the predicted MVI- group than that in the predicted MVI + group. CONCLUSIONS: In this study, we identified a cfDNA methylation signature for HCC detection and a tissue DNA methylation signature for MVI status prediction wit...