Evidence map›Paper›PMID 35115564›Full record

ArticleScientific reports2022

Well-differentiated liver cancers reveal the potential link between ACE2 dysfunction and metabolic breakdown.

Lise Desquilles, Luis Cano, Gevorg Ghukasyan, Nicolas Mouchet, Clémence Landreau, Anne Corlu, Bruno Clément, Bruno Turlin, Romain Désert, Orlando Musso

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. 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
1.3field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. SARS-CoV-2 receptor ACE2 is upregulated by fatty acids in human MASH.JHEP reports : innovation in hepatology · 2024
    Article
  4. Review
  5. Metabolic Networks: Weighted Gene Correlation Network Analysis.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
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

10 authors at 3 institutions in 1 country.

Lise DesquillesINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Luis CanoINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Gevorg GhukasyanUniversity of Rennes, CNRS, INSERM, UMS Biosit, Core Facility H2P2, 35000, Rennes, France.
Nicolas MouchetUniversity of Rennes, CNRS, INSERM, UMS Biosit, Core Facility H2P2, 35000, Rennes, France.
Clémence LandreauINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Anne CorluINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Bruno ClémentINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Bruno TurlinINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Romain DésertINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.
Orlando MussoINSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France. orlando.musso@inserm.fr.
Inserm · FRCentre National de la Recherche Scientifique · FRFoie, Métabolisme, Cancer · FR

Funding

Institut National Du Cancer 12688
6 · The paper itself

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the receptor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing Coronavirus disease 2019 (COVID-19). Transmembrane serine protease 2 (TMPRSS2) is a coreceptor. Abnormal hepatic function in COVID-19 suggests specific or bystander liver disease. Because liver cancer cells express the ACE2 viral receptor, they are widely used as models of SARS-CoV-2 infection in vitro. Therefore, the purpose of this study was to analyze ACE2 and TMPRSS2 expression and localization in human liver cancers and in non-tumor livers. We studied ACE2 and TMPRSS2 in transcriptomic datasets totaling 1503 liver cancers, followed by high-resolution confocal multiplex immunohistochemistry and quantitative image analysis of a 41-HCC tissue microarray. In cancers, we detected ACE2 and TMPRSS2 at the biliary pole of tumor hepatocytes. In whole mount sections of five normal liver samples, we identified ACE2 in hepatocyte's bile canaliculi, biliary epithelium, sinusoidal and capillary endothelial cells. Tumors carrying mutated β-catenin showed ACE2 DNA hypomethylation and higher mRNA and protein expression, consistently with predicted β-catenin response sites in the ACE2 promoter. Finally, ACE2 and TMPRSS2 co-expression networks highlighted hepatocyte-specific functions, oxidative stress and inflammation, suggesting a link between inflammation, ACE2 dysfunction and metabolic breakdown.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2beta CateninCarcinoma, HepatocellularDNA MethylationGene ExpressionHepatocytesHumansInflammationLiver NeoplasmsMutationOxidative StressReceptors, VirusRNA, MessengerSerine EndopeptidasesACE2 protein, humanAngiotensin-Converting Enzyme 2beta CateninReceptors, VirusRNA, MessengerSerine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID35115564
PMCPMC8814043
OpenAlexW4226253391

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.