Evidence map›Paper›PMID 41895279›Full record

ArticleCancer cell2026

Molecular insights into early malignant transition of hepatocellular carcinoma.

Zhengtao Zhang, Hong Li, Lingli Chen, Tao Lu, Xinyi Shentu, Yuanhua Liu, Zhixuan Tang, Shuyi Ji, Zhixin Qiu, Yining Zou and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Zhengtao ZhangThe Research Laboratory of Liver Molecular Pathology, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, P.R. China; University of Chinese Academy of Sciences, Beijing 101408, P.R. China.
Hong LiShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China. Electronic address: lihong01@sibs.ac.cn.
Lingli ChenDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Tao LuDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, P.R. China.
Xinyi ShentuSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P.R. China.
Yuanhua LiuState Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Zhixuan TangShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Shuyi JiInstitute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, P.R. China.
Zhixin QiuDepartment of Anesthesiology, Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, P.R. China.
Yining ZouDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Hong WenDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Jing HanDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Zhengzeng JiangDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Jie FanDepartment of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Xinbo GaoThe Research Laboratory of Liver Molecular Pathology, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, P.R. China; University of Chinese Academy of Sciences, Beijing 101408, P.R. China.
Dianfan LiThe Research Laboratory of Liver Molecular Pathology, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Agavni MesropianLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.
Roser PinyolLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.
Josep M LlovetLiver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
Hui DongDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, P.R. China.
Yuan JiDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China. Electronic address: ji.yuan@zs-hospital.sh.cn.
Lijian HuiThe Research Laboratory of Liver Molecular Pathology, Key Laboratory of Multi-cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, P.R. China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P.R. China. Electronic address: ljhui@sibcb.ac.cn.

Funding

The Role of KLF6 in Hepatic FibrosisR01DK056621 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FRIEDMAN, SCOTT L. · 2000 to 2019
$6.2M
Hepatic stellate cells in NASH fibrosis and HCCR01DK128289 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCOTT L. FRIEDMAN · 2021 to 2026
$2.6M
Determinants of immunotherapy response in NASH-Hepatocellular carcinomaR01CA273932 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JOSEP M LLOVET · 2023 to 2026
$2.0M
NCI NIH HHS R01 CA273932NIDDK NIH HHS R01 DK056621NIDDK NIH HHS R01 DK128289
6 · The paper itself

Abstract

Understanding the molecular drivers of the premalignant-to-malignant transition is essential for early cancer detection and intervention, yet this process remains poorly characterized due to limited access to evolutionarily related lesions. Here, we comprehensively profiled the genomic and immunological landscapes of 21 very early hepatocellular carcinomas (veHCCs) arising within 17 cancer-prone dysplastic nodules (DNs). Notably, 82% of cancer-prone DNs harbored TERT alterations, suggesting a predisposing rather than causative role of TERT alteration in malignant transition. Notably, the accumulation of copy number alterations (CNAs), rather than single-nucleotide variants, is strongly associated with malignant transition. Intriguingly, different from the paradigm that HCC arises in chronic inflammation, cancer-prone DNs displayed immune inactivity. Strikingly, 43% of veHCCs showed an inflamed yet immune-evasive phenotype. These findings propose two evolutionary scenarios of early hepatocarcinogenesis, CNA-dominant progression and inflamed progression with early immune evasion, underscoring the potential of immunotherapy for early intervention.

Indexed as

Carcinoma, HepatocellularCell Transformation, NeoplasticLiver NeoplasmsDisease ProgressionDNA Copy Number VariationsGene Expression Regulation, NeoplasticHumansTelomeraseTelomeraseTERT protein, humancancercopy number alterationearly carcinogenesisevolutionary trajectorieshepatocellular carcinomaImmune evasionmalignant transitionresponse to immune therapiesspatial transcriptomicstumor heterogeneity

Identifiers

PMID41895279
PMCPMC13665580

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.