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
Abstract
BACKGROUND

There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma (HCC). Studies, mostly from the Asian-Pacific region, demonstrated differential expression of liver-specific microRNA-122 (miR-122) in tissue as well as in sera of patients with hepatitis B virus- and hepatitis C virus-induced HCC.

AIM

To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera.

METHODS

Patients with confirmed HCC (n = 91) were included in the study over a two-year period. Patients were characterized according to Child-Pugh score, Barcelona clinic liver cancer (BCLC) staging system, etiology of liver disease, laboratory parameters and overall survival. MiR-122 was measured in sera using TaqMan assay normalized to spiked-in cel-miR-39.

RESULTS

Serum miR-122 quantity was independent of the Child-Pugh score, the BCLC stage or the underlying etiology. Significant positive correlation was found between miR-122 and alanine aminotransferase (P < 0.0001), aspartate aminotransferase (P = 0.0001), alpha-fetoprotein (AFP) (P = 0.0034) and hemoglobin concentration (P = 0.076). Negative correlation was observed between miR-122 level and creatinine concentration (P = 0.0028). AFP, Child-Pugh score and BCLC staging system were associated with survival differences. In overall cohort low miR-122 in sera was only associated with a trend for a better overall survival without reaching statistical significance. Subgroup analysis revealed that low miR-122 was significantly associated with better prognosis in patients with advanced cirrhosis (Child-Pugh class B/C), advanced tumor stage (BCLC B/C/D) and normal AFP (< 7 ng/mL).

CONCLUSION

Our results strongly support the value of miR-122 as potential biomarker of liver injury and probably prognosis. Nevertheless, the value of miR-122 in prediction of prognosis of HCC patients was limited to certain patients’ subgroups. Since circulating miR-122 may be influenced by impaired renal function, AFP and hemoglobin concentration, those factors need to be considered while interpreting miR-122 level.

Keywords: Hepatocellular carcinoma; MicroRNA; Prognosis; MicroRNA-122; Influencing factors

Core tip: Small non-coding RNAs are in focus of liver biomarker research. Here we confirm that the most abundant liver-specific microRNA-122 (miR-122) is a potential biomarker for liver injury and has potential value to predict the outcome of patients with hepatocellular carcinoma, but several influencing factors need to be taken into account while interpreting the miR-122 level. Besides clinical aspects, several coexisting factors like impairment of renal function, hemoglobin concentration, alpha-fetoprotein level and liver injury may strongly influence circulating miR-122 level and potential clinical translational application of miR-122.