Evidence map›Paper›PMID 25945129›Full record

ArticleClinical epigenetics2015

DNA methylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma.

Silvia Udali, Patrizia Guarini, Andrea Ruzzenente, Alberto Ferrarini, Alfredo Guglielmi, Valentina Lotto, Paola Tononi, Patrizia Pattini, Sara Moruzzi, Tommaso Campagnaro and 6 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% of its field
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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).International journal of molecular medicine · 2025
    Review
  7. Article
  8. Article
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  11. DNA methylation markers in the detection of hepatocellular carcinoma.European journal of cancer (Oxford, England : 1990) · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Polyphenols as Potent Epigenetics Agents for Cancer.International journal of molecular sciences · 2022
    Review
  17. Article
  18. Human Orphan Cytochromes P450: An Update.Current drug metabolism · 2022
    Article
  19. Review
  20. 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

16 authors at 2 institutions in 2 countries.

Silvia UdaliDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Patrizia GuariniDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Andrea RuzzenenteDepartment of Surgery, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Alberto FerrariniDepartment of Biotechnology, Genetics and Heredity Section, University of Verona School of Agroindustrial Biotechnology, Ca' Vignal 1, Strada Le Grazie 15, 37134 Verona, Italy.
Alfredo GuglielmiDepartment of Surgery, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Valentina LottoDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Paola TononiDepartment of Biotechnology, Genetics and Heredity Section, University of Verona School of Agroindustrial Biotechnology, Ca' Vignal 1, Strada Le Grazie 15, 37134 Verona, Italy.
Patrizia PattiniDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Sara MoruzziDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Tommaso CampagnaroDepartment of Surgery, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Simone ConciDepartment of Surgery, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Oliviero OlivieriDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Roberto CorrocherDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
Massimo DelledonneDepartment of Biotechnology, Genetics and Heredity Section, University of Verona School of Agroindustrial Biotechnology, Ca' Vignal 1, Strada Le Grazie 15, 37134 Verona, Italy.
Sang-Woon ChoiFriedman School of Nutrition Science and Policy Tufts University, 150 Harrison Ave, Boston, MA 02111 USA ; Chaum Life Center, CHA University, 4-1, Cheongdam-dong, Gangnam-gu, 135-948 Seoul, Korea.
Simonetta FrisoDepartment of Medicine, University of Verona School of Medicine, Policlinico 'G.B. Rossi', P.le L.A. Scuro, 10, 37134 Verona, Italy.
University of Verona · ITTufts University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlcohol is a well-known risk factor for hepatocellular carcinoma (HCC), but the mechanisms underlying the alcohol-related hepatocarcinogenesis are still poorly understood. Alcohol alters the provision of methyl groups within the hepatic one-carbon metabolism, possibly inducing aberrant DNA methylation. Whether specific pathways are epigenetically regulated in alcohol-associated HCC is, however, unknown. The aim of the present study was to investigate the genome-wide promoter DNA methylation and gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients undergoing curative surgery, array-based DNA methylation and gene expression data of all annotated genes were analyzed by comparing HCC tissue and homologous cancer-free liver tissue.

resultsAfter merging the DNA methylation with gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced, and 56 hypomethylated-repressed genes. Notably, promoter DNA methylation emerged as a novel regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolism (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16), iron homeostasis (HAMP), one-carbon metabolism (SHMT1), and genes with a putative, newly identified function as tumor suppressors (FAM107A, IGFALS, MT1G, MT1H, RNF180).

conclusionsA genome-wide DNA methylation approach merged with array-based gene expression profiles allowed identifying a number of novel, epigenetically regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically regulated through promoter DNA methylation in alcohol-associated HCC. Due to the reversibility of epigenetic mechanisms by environmental/nutritional factors, these findings may open up to novel interventional strategies for hepatocarcinogenesis prevention in HCC related to alcohol, a modifiable dietary component.

Indexed as

AlcoholCandidate tumor-suppressor genesDNA methylationEpigeneticsGene expression arrayHepatocellular carcinomaMeDIP-chipOne-carbon metabolismRetinol metabolism

Identifiers

PMID25945129
PMCPMC4419480
OpenAlexW1984303873

What OpenQuestion holds

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LicenceCC BY
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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.