Evidence map›Paper›PMID 42480815›Full record

ArticleJHEP reports : innovation in hepatology2026

cfDNA-derived gene signatures as surrogate for microvascular invasion in HCC.

Ruijie Gong, Linchen Wang, Dongdong Xue, Jiabin Cai, Yurou Jiang, Jianhang Huang, Jinjin Zhu, Zhongchen Li, Aiwu Ke, Guoming Shi and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Ruijie GongDepartment of Liver Surgery and Transplantation, Zhongshan Hospital (Xiamen Branch), Xiamen, Fujian, China; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Linchen WangDepartment of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Dongdong XueThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Jiabin CaiDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Yurou JiangSchool of Computer and Computing Science, Hangzhou City University, Hangzhou, Zhejiang, China.
Jianhang HuangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Jinjin ZhuDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Zhongchen LiDepartment of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Aiwu KeDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Guoming ShiDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Jie WangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Wentao WangDepartment of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiaping ZhengDepartment of Interventional Therapy, Zhejiang Cancer Hospital, Institute of Hangzhou Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Weijian YangDepartment of General Surgery, The People's Hospital of Pingyang County, Pingyang Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhou ZhangDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Jian ZhouDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Jia FanDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Shanghai, China.
Wei ZhangDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: wei.zhang1@northwestern.edu.
Pingting GaoEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: gao.pingting@zs-hospital.sh.cn.
Lei ChenThe International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Electronic address: chenlei@smmu.edu.cn.
Danjun SongDepartment of Interventional Therapy, Zhejiang Cancer Hospital, Institute of Hangzhou Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China. Electronic address: songdanjun@hotmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsMicrovascular invasion (MVI) is a critical prognostic risk factor in hepatocellular carcinoma (HCC). We evaluated the performance of 5-hydroxymethylcytosine (5hmC) modifications in circulating cell-free DNA (cfDNA) in preoperative assessment of MVI.

methodsA total of 907 patients with HCC were enrolled from two centers, including 671 in the training cohort, 152 in the internal validation cohort, and 84 in the external validation cohort. Preoperative clinical data, laboratory parameters, and cfDNA-derived 5hmC profiles were collected. Feature selection was performed using XGBoost, and modeling was conducted using a multilayer perceptron neural network. Survival analyses were performed to evaluate the prognostic significance of the MVI prediction model. RNA sequencing analysis was performed to explore the potential mechanism underlying the proposed model.

resultsThe 181-5hmC-modification signature demonstrated strong discriminatory performance, achieving an area under the curve of 0.852, 0.862, and 0.864 in the training, internal validation, and external validation cohorts, respectively. Univariate and multivariate analyses identified the alpha-fetoprotein level (odds ratio [OR] 1.576, p = 0.039), Barcelona Clinic Liver Cancer stage (OR 3.051, p <0.001), and the 5hmC signature (OR 46.891, p <0.001) as independent predictors of MVI. The 5hmC signature demonstrated significantly higher predictive accuracy than alpha-fetoprotein levels or BCLC stage alone. Survival analysis showed that the 5hmC signature significantly stratified both recurrence-free and overall survival in patients with resectable HCC. Furthermore, interpretability analysis based on RNA sequencing revealed that lower MVI prediction scores were associated with immune-related pathways and immune infiltration levels.

conclusionsWe developed and validated a circulating cfDNA-derived 5hmC signature that non-invasively predicts preoperative MVI status, with potential clinical utility in the management of resectable HCC. IMPACT AND IMPLICATIONS: In this study, we present the first integration of cfDNA-derived 5hmC profiling with machine learning for preoperative MVI prediction in resectable HCC. The proposed 5hmC signature demonstrates potential for predicting MVI status and prognosis before surgery. Integration of RNA sequencing analysis provides biological support for the model's predictions, strengthening its clinical relevance. As a blood-based assay, this approach offers practical advantages for potential routine clinical implementation.

Indexed as

5hmCcfDNAHepatocellular carcinomaMicrovascular invasionPrognosis

Identifiers

PMID42480815
PMCPMC13598192

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.