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

Lise Desquilles1, Luis Cano1, Gevorg Ghukasyan2

  • 1INSERM, INRAE, University of Rennes, Nutrition Metabolisms and Cancer, Rennes, France.

Scientific Reports
|February 4, 2022
PubMed

Insights

This study investigated Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) in liver cancer. Findings reveal their expression in tumor hepatocytes, linking inflammation and metabolic dysfunction in liver disease.

Area of Science:

  • Hepatology
  • Virology
  • Oncology

Background:

  • Angiotensin-converting enzyme 2 (ACE2) is the SARS-CoV-2 receptor, and TMPRSS2 is a coreceptor.
  • COVID-19 can cause abnormal liver function, indicating potential liver disease.
  • Liver cancer cells express ACE2, making them useful models for SARS-CoV-2 infection studies.

Purpose of the Study:

  • To analyze the expression and localization of ACE2 and TMPRSS2 in human liver cancers and non-tumor liver tissues.
  • To investigate the relationship between ACE2 expression and tumor characteristics, including beta-catenin mutations.
  • To explore the functional implications of ACE2 and TMPRSS2 co-expression in the liver.

Main Methods:

  • Analysis of transcriptomic datasets from 1503 liver cancers.
  • High-resolution confocal multiplex immunohistochemistry on a 41-HCC tissue microarray.
  • Quantitative image analysis of protein expression and localization.

Main Results:

  • ACE2 and TMPRSS2 were detected at the biliary pole of tumor hepatocytes.
  • ACE2 was identified in normal liver cells, including hepatocytes, biliary epithelium, and endothelial cells.
  • Mutated beta-catenin in tumors correlated with ACE2 DNA hypomethylation and increased ACE2 expression.
  • Co-expression networks indicated roles in hepatocyte-specific functions, oxidative stress, and inflammation.

Conclusions:

  • ACE2 and TMPRSS2 are expressed in human liver cancer and normal liver tissues.
  • Beta-catenin mutations influence ACE2 expression in liver cancer.
  • ACE2 and TMPRSS2 co-expression suggests a link between inflammation, ACE2 dysfunction, and metabolic breakdown in the liver.

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