Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
- Author:
Suqin YANG
1
;
Sunbin LING
;
Jianhua LI
;
Yan WANG
;
Jiapei WANG
;
Qiwei HUANG
;
Fanming LIU
;
Yiqi ZHUANG
;
Yingyu ZHENG
;
Rui WANG
;
Zhe YANG
;
Xiaoping ZHENG
;
Kai WANG
;
Zhikun LIU
;
Jun CHEN
;
Jianguo WANG
;
Haiyang XIE
;
Lin ZHOU
;
Leiming CHEN
;
Guoqiang CAO
;
Dandan CHEN
;
Junfang JI
;
Bin ZHAO
;
Chao JIANG
;
Di LU
;
Xuyong WEI
;
Hangjin JIANG
;
Qiaonan SHAN
;
Hengbo SHI
;
Yong-Zhen XU
;
Shusen ZHENG
;
Zhengxin WANG
;
Shengda LIN
;
Xiao XU
Author Information
- Publication Type:Original Article
- From:Clinical and Molecular Hepatology 2026;32(2):884-903
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background/Aims:Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion:Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
