Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma

作者：Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biaohua Wu, Xueyi Gong, Wenjing Zhou, Yu‐Long Xie, Yun Du, Quan Wen, Panpan Wang, Li Deng, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu, Mingfang Ji, Zongli Zheng · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.109701 · 被引用次数：6 · 研究领域：Cancer Genomics and Diagnostics、Hepatocellular Carcinoma Treatment and Prognosis、Genetic factors in colorectal cancer

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC.