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Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity

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Abstract

Apelin, a peptide of 77 amino acids, and its endogenous ligand, angiotensin-like-receptor 1 (APJ), play a key role in the development of tumors by enhancing angiogenesis, metastasis, cell proliferation, development of cancer stem cells and drug resistance and inhibiting apoptosis of cancer cells. However, little is known about Apelin/APJ system involvement in hepatocellular carcinoma (HCC). The aim of this study was to evaluate Apelin and APJ expression in liver specimens, obtained from subjects with HCV-positive HCC who underwent liver transplantation, according to liver disease severity (liver recipients, LR, n = 14, age 59.4 ± 1.8) and in donors (liver donors, LD, n = 14, age 62.1 ± 17.3). Apelin/APJ axis, apoptotic and inflammatory markers were evaluated by Real-Time PCR analysis. The Apelin/APJ system expression resulted significantly higher in LR in comparison with LD (p < 0.05), in particular in those with more severe liver disease. The apoptotic (Bcl-2, BAX, NOTCH-1, Casp-3) and inflammatory (IL-6, TNF-α) markers were increased as a function of disease severity (p < 0.05). Multiple significant positive correlations were found between Apelin/APJ axis and the other markers. Although further investigations are needed to better understand the role of Apelin/APJ axis in HCC, our result indicated a potential role of this axis in its development and progression as well as in recognizing novel therapeutic targets opening a new avenue for treatment.

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Funding

This work was supported by “INTEROMICS FLAGSHIP PROJECT” (Metabolomics identification of prognostic and diagnostic biomarkers of hepatocellular carcinoma), supported by the MIUR (Italian Ministry of Education, University and Research) and coordinated by the CNR (National Research Council, Principal Investigator: Dr. Amalia Gastaldelli).

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Authors and Affiliations

  1. CNR Institute of Clinical Physiology, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy

    Manuela Cabiati, Melania Gaggini & Silvia Del Ry

  2. Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy

    Paolo De Simone

Authors
  1. Manuela Cabiati
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  2. Melania Gaggini
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  3. Paolo De Simone
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  4. Silvia Del Ry
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Contributions

SDR contributed to conceptualization, data curation and formal analysis. SDR, MC and MG helped with methodology. PDS contributed to patient enrolment. SDR writes the original draft. MC and MG contributed to writing—review & editing.

Corresponding author

Correspondence to Silvia Del Ry.

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All patients enrolled gave their consent to be included in the study.

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The study was carried out in compliance with the principles set forth in the 2008 Seoul revision of the Declaration of Helsinki. Approval was obtained from the Institutional Ethics Committee.

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Cabiati, M., Gaggini, M., De Simone, P. et al. Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity. Clin Exp Med 21, 269–275 (2021). https://doi.org/10.1007/s10238-020-00672-x

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  • DOI: https://doi.org/10.1007/s10238-020-00672-x

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