Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2020; 12(11): 1031-1045
Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1031
Circulating miR-21-5p level has limited prognostic value in patients with hepatocellular carcinoma and is influenced by renal function
Martin Franck, Cosima Thon, Kerstin Schütte, Peter Malfertheiner, Alexander Link
Martin Franck, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, Germany
Martin Franck, Cosima Thon, Kerstin Schütte, Peter Malfertheiner, Alexander Link, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg 39120, Germany
Kerstin Schütte, Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück 49074, Germany
Author contributions: Franck M performed the experiments; Schütte K and Malfertheiner P provided the clinical material; Franck M, Thon C, and Link A carried out the analysis and interpretation of the data and drafting of the manuscript; Link A created the study concept and design and is the guarantor of the study; All authors edited and approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the ethical board of the Otto-von-Guericke University (Study number 99/10).
Informed consent statement: The study was performed according to the principle of the Declaration of Helsinki. The study was approved by Institutional Review Board of Otto-von-Guericke University Magdeburg No. 99/10. All patients provided written informed consent.
Conflict-of-interest statement: Authors declare that they have no potential conflicts of interest.
Data sharing statement: Technical appendix and dataset available from the corresponding author: alexander.link@med.ovgu.de. Participants gave informed consent for data analysis and publication. Certain restriction may apply in accordance to patient´s consent.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alexander Link, MD, PhD, Academic Research, Associate Professor, Doctor, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Leipziger Street 44, Magdeburg 39120, Germany. alexander.link@med.ovgu.de
Received: June 11, 2020
Peer-review started: June 12, 2020
First decision: July 30, 2020
Revised: August 15, 2020
Accepted: September 18, 2020
Article in press: September 18, 2020
Published online: November 27, 2020
ARTICLE HIGHLIGHTS
Research background

MiR-21-5p (miR-21) is one of the most frequently deregulated microRNAs (miRNAs) in tissue and in body fluids in different diseases and most importantly in cancer. Overexpression and prognostic value of tissue miR-21 in hepatocellular carcinoma (HCC) has been previously suggested, but the data are heterogeneous. Greatest evidence in support of miR-21 as a biomarker originate from Asian population, highlighting the need for additional scientific effort and search for potential confounding factors including etiological background of HCC.

Research motivation

Data on prognostic value of serum miR-21 in patients with mainly alcohol abuse-induced HCC as well as the knowledge of potential influencing factors and underlying mechanism are still limited.

Research objectives

We evaluated the prognostic value of serum miR-21 in a European cohort of HCC patients with mainly alcohol-associated liver disease in real-life settings. We also explored the potential confounding clinical or laboratory influencing factors on the serum miR-21 levels.

Research methods

Circulating miR-21 level were analyzed in 91 sera samples from well-characterized patients with HCC. Clinical and laboratory parameters (including alpha-fetoprotein), miR-122 as well as the overall survival (OS) were examined.

Research results

We observed no association between serum miR-21 and OS, Child-Pugh scores, or BCLC staging data. Significant correlation between serum miR-21 and aspartate aminotransferase, International Normalized Ratio, creatinine, and hsa-miR-122 suggested the potential influence of liver and renal function on circulating miR-21 levels.

Research conclusions

Our data do not support prognostic role of miR-21 in HCC patients. An association of miR-21 with surrogate markers of liver injury and renal function strongly support the need for better understanding of influencing factors in miRNA biogenesis.

Research perspectives

Systematic profiling studies that provide overall data assessment of miRNAs in view of potential influencing factors in blood are needed prior clinical implementation of miRNAs as clinical biomarkers.