Detection and monitoring of HBV-related hepatocellular carcinoma from plasma cfDNA fragmentation profiles

Most hepatocellular carcinomas (HCCs) are associated with hepatitis B virus infection (HBV) in China. Early detection of HCC can significantly improve prognosis but is not yet fully clinically feasible. This study aims to develop methods for detecting HCC and studying the carcinogenesis of HBV using...

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Bibliographic Details
Published in:	Genomics (San Diego, Calif.) Vol. 114; no. 6; p. 110502
Main Authors:	Sun, Xinfeng, Feng, Wenxing, Cui, Pin, Ruan, Ruyun, Ma, Wenfeng, Han, Zhiyi, Sun, Jialing, Pan, Yuanke, Zhu, Jinxin, Zhong, Xin, Li, Jing, Ma, Mengqing, Hu, Rui, Lv, Minling, Huang, Qi, Zhang, Wei, Feng, Mingji, Zhuang, Xintao, Huang, Bingding, Zhou, Xiaozhou
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-11-2022
Subjects:	Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - genetics cfDNA China ctDNA Fragmentation profile Hepatocellular carcinoma Humans Liver Neoplasms - diagnosis Liver Neoplasms - genetics Machine learning China WGS cfDNA Machine learning Hepatocellular carcinoma HCC HCV Fragmentation profile HBV ctDNA
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Summary:	Most hepatocellular carcinomas (HCCs) are associated with hepatitis B virus infection (HBV) in China. Early detection of HCC can significantly improve prognosis but is not yet fully clinically feasible. This study aims to develop methods for detecting HCC and studying the carcinogenesis of HBV using plasma cell-free DNA (cfDNA) whole-genome sequencing (WGS) data. Low coverage WGS was performed for 452 participants, including healthy individuals, hepatitis B patients, cirrhosis patients, and HCC patients. Then the sequencing data were processed using various machine learning models based on cfDNA fragmentation profiles for cancer detection. Our best model achieved a sensitivity of 87.10% and a specificity of 88.37%, and it showed an increased sensitivity with higher BCLC stages of HCC. Overall, this study proves the potential of a non-invasive assay based on cfDNA fragmentation profiles for the detection and prognosis of HCC and provides preliminary data on the carcinogenic mechanism of HBV. •Each of four cohorts harbours unique cfDNA fragmentation profile, indicating potential biomarker for cancer early detection.•cfDNA fragmentation profiles vary between relapse and non-relapse groups of HCC patients.•HBV integration cause specific cfDNA epigenomic alterations to host genome, which can be eased after antiviral therapy.•cfDNA fragmentation profiles predict significant portion of hepatitis B and cirrhosis patient have early signs of HCC.
ISSN:	0888-7543 1089-8646
DOI:	10.1016/j.ygeno.2022.110502