Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures

作者：Rong Fan, Lei Chen, Siru Zhao, Hao Yang, Zhengmao Li, Yun-Song Qian, Hong Ma, Xiaolong Liu, Chuanxin Wang, Xieer Liang, Jian Bai, Jianping Xie, Xiaotang Fan, Qing Xie, Xin Hao, Chunying Wang, Yang Song, Yanhang Gao, Honglian Bai, Xiaoguang Dou, Jingfeng Liu, Lin Wu, Guoqing Jiang, Qi Xia, Dan Zheng, Huiying Rao, Jie Xia, Jia Shang, Pujun Gao, Dong‐Ying Xie, Yan-Long Yu, Yongfeng Yang, Hongbo Gao, Yali Liu, Aimin Sun, Yongfang Jiang, Yanyan Yu, Junqi Niu, Jian Sun, Hongyang Wang, Jinlin Hou · 发表于：Journal of Hepatology · 年份：2023 · DOI：10.1016/j.jhep.2023.05.039 · 被引用次数：42 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Ferroptosis and cancer prognosis、Cancer Genomics and Diagnostics

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the predic...