Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2020; 26(1): 86-96
Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.86
Prognostic value of serum microRNA-122 in hepatocellular carcinoma is dependent on coexisting clinical and laboratory factors
Martin Franck, Kerstin Schütte, Peter Malfertheiner, Alexander Link
Martin Franck, Kerstin Schütte, Peter Malfertheiner, Alexander Link, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg 39120, Germany
Martin Franck, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, 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 clinical material; Franck M, Malfertheiner P and Link A did 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.
Informed consent statement: In this study we used retrospectively collected anonymized samples from a previous study. No additional informed consent other than from the primary study was obtained. Ethical committee approved the study protocol.
Conflict-of-interest statement: Alexander Link is principle investigator of the “LiLife”-Project supported by the funds of European Commission through the “Europäischer Fond für regionale Entwicklung” (EFRE) as well as by the regional Ministry of Economy, Science and Digitalization as part of the “Autonomie im Alter” research group. Other authors declare that they have no potential conflicts of interest.
Data sharing statement: Technical appendix and dataset available from the corresponding author at alexander.link@med.ovgu.de. Participants gave informed consent for data analysis and publication. Since no patients consent to data sharing was obtained, no additional data will be made available. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Open-Access: This 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 Non Commercial (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, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Leipziger Str. 44, Magdeburg 39120, Germany. alexander.link@med.ovgu.de
Received: September 2, 2019
Peer-review started: September 2, 2019
First decision: October 14, 2019
Revised: December 4, 2019
Accepted: December 13, 2019
Article in press: December 13, 2019
Published online: January 7, 2020
Processing time: 126 Days and 10.8 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is among the deadliest conditions worldwide. One of the challenges related to HCC is the identification of specific and sensitive diagnostic and prognostic biomarkers. MicroRNAs have been shown to be deregulate in HCC and microRNA-122 (miR-122) is among the most promising liver-specific molecules.

Research motivation

miR-122 has been studied in Asian-Pacific regions but only limited knowledge is available from European population. At present the role of miR-122 as prognostic is not independently validated. Most importantly, it is still less known about potential factors that may influence miR-122 level in blood samples.

Research objectives

Circulating miR-122 may be influenced by impaired renal function, alpha-fetoprotein (AFP) and hemoglobin concentration. Those factors may strongly influence the performance of miR-122 a potential biomarker in HCC.

Research methods

A cohort of well characterized patients with HCC were included in this study. Quantitative TaqMan assay was used to analyze miR-122 in serum and the results were normalized to spiked-in cel-miR-39. The data were stratified based on individual characteristics including liver disease, liver biochemistry, tumor staging and overall survival.

Research results

Overall miR-122 was shown to be independent to Child-Pugh score, Barcelona clinic liver cancer tumor staging classification or etiology of liver disease. Among the studied factors, we identified alanine aminotransferase, aspartate aminotransferase, AFP and renal function (creatinine) as factors that may influence miR-122 level in serum. According to our results, low miR-122 may be associated with lower overall survival, however, only if certain conditions including cirrhosis score, tumor stage or APF are considered.

Research conclusions

The results from this study strongly suggest that renal function and liver inflammation may impact microRNA biomarkers. In particular, a liver-specific miR-122 may be strongly influenced by intrahepatic inflammation which may create potential bias. Our results support the use of miR-122 as a marker for liver inflammation. The value of miR-122 in prediction of overall survival is, however, limited due to the co-existing factors. Further studies will need to determine the mechanism responsible for the influence, but also find a way of controlling the influencing factors in biomarker studies.

Research perspectives

This study clearly highlights the need for better understanding of microRNAs biogenesis in circulation. Since large number of studies focus on microRNAs as potential biomarkers, we urge for better characterization of co-existing factors to identify potential individual influencing factors. Future studies related to miR-122 need to consider also renal function and liver biochemistry.