Evidence map›Paper›PMID 41390797›Full record

ArticleCommunications biology2025

Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential.

Clooney C Y Cheng, Ming Fung Cheung, Ah Young Lee, Qiong Wu, Savio Ho-Chit Chow, Julie Y J Ang, Ignacio Riquelme Medina, Grace Lo, Haoran Wu, Weiqin Yang and 4 more

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Translational cancer research · 2026
    Article
  2. Article
  3. Article
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  5. Review
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

14 authors.

Clooney C Y ChengDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0003-2206-3283
Ming Fung CheungCenter for Epigenomics Research, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0001-8368-3190
Ah Young LeeCenter for Epigenomics Research, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Qiong WuSchool of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Savio Ho-Chit ChowCancer Genome and Epigenetics Program, NCI-Designated Cancer Centre, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8994-8727
Julie Y J AngDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Ignacio Riquelme MedinaDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.ORCID http://orcid.org/0000-0002-8631-7636
Grace LoCenter for Epigenomics Research, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Haoran WuSchool of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Weiqin YangSchool of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.ORCID http://orcid.org/0000-0002-3564-9104
Paul B S LaiDepartment of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.ORCID http://orcid.org/0000-0002-9469-6728
Kevin Y YipCancer Genome and Epigenetics Program, NCI-Designated Cancer Centre, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. kyip@sbpdiscovery.org.ORCID http://orcid.org/0000-0001-5516-9944
Alfred S ChengSchool of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. alfredcheng@cuhk.edu.hk.ORCID http://orcid.org/0000-0003-2345-6951
Danny LeungDivision of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. dcyleung@ust.hk.ORCID http://orcid.org/0000-0002-2472-894X

Funding

Croucher Foundation CIA16SC02Research Grants Council, University Grants Committee (RGC, UGC) 16103721
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and has limited therapeutic options. Epigenetic dysregulation plays a crucial role in hepatocarcinogenesis; however, its impact on cis-regulatory elements (CREs) and retrotransposons remains underexplored. Here, we investigated the epigenetic changes underlying the aberrant CRE and retrotransposon activity in HCC. We show that focal DNA hypomethylation of these elements is associated with transcriptional reprogramming. Notably, we uncover a dual regulatory mechanism for GPC3, a key diagnostic biomarker and immunotherapeutic target in HCC. This requires the concomitant reactivation of a fetal liver super-enhancer (SE) and DNA hypomethylation of CpG islands. Furthermore, DNA methylation loss drives cryptic activation of retrotransposons, some of which exhibit prognostic potential. Intriguingly, we identify a HERVE-int-derived long non-coding RNA that shows higher expression in patients with more aggressive tumors, poorer disease outcomes, and is correlated with molecular signatures associated with improved response to immunotherapy. Collectively, our findings reveal widespread epigenomic dysregulation of CREs and retrotransposons in HCC, highlighting new potential therapeutic strategies and biomarkers.

Indexed as

Carcinoma, HepatocellularGene Expression Regulation, NeoplasticLiver NeoplasmsRegulatory Sequences, Nucleic AcidRetroelementsBiomarkers, TumorCell Line, TumorCpG IslandsDNA MethylationEpigenesis, GeneticGlypicansHumansMultiomicsPrognosisRNA, Long NoncodingBiomarkers, TumorGlypicansGPC3 protein, humanRetroelementsRNA, Long Noncoding

Identifiers

PMID41390797
PMCPMC12717160

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.