Case Control Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2017; 23(21): 3864-3875
Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3864
Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients
Moustafa Nouh Elemeery, Ahmed Noah Badr, Marwa Anwar Mohamed, Doaa Ahmed Ghareeb
Moustafa Nouh Elemeery, Medical Biotechnology Laboratory, Genetic Engineering and Biotechnology Research Division, National Research Centre, Cairo 12622, Egypt
Ahmed Noah Badr, Toxicology and Food Contaminant Laboratory, Food Science and Nutrition Research Division, National Research Centre, Cairo 12622, Egypt
Marwa Anwar Mohamed, Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria 21511, Egypt
Doaa Ahmed Ghareeb, Molecular Biology Laboratory, Faculty of Science, Alexandria University, Alexandria 21511, Egypt
Author contributions: Elemeery MN was the main author in this work as he performed the majority of experiments and wrote the manuscript; Ghareeb DA participated in work design and manuscript editing; Badr AN provided analytical tools; Mohamed MA collected the human samples, provided analytical tools and wrote the patient consent form; all authors shared in the performance of manuscript revision and data revision.
Institutional review board statement: The study was approved by the Ethics Committee of Theodor Bilharz (Giza, Egypt).
Informed consent statement: All patients provided informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at mn.badr@nrc.sci.eg.
Open-Access: This article is an open-access article which 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/
Correspondence to: Moustafa Nouh Elemeery, MSc, Laboratory of Medical Biotechnology, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, Cairo 12622, Egypt. mn.badr@nrc.sci.eg
Telephone: +20-1005013630 Fax: +20-233370931
Received: November 29, 2016
Peer-review started: December 1, 2016
First decision: December 28, 2016
Revised: January 18, 2017
Accepted: March 2, 2017
Article in press: March 2, 2017
Published online: June 7, 2017
Abstract
AIM

To investigate the prospective importance of serum micro (mi)RNAs (miR-125b, miR-138b, miR-1269, miR-214-5p, miR-494, miR375 and miR-145) as early biomarkers for the diagnosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).

METHODS

Two-hundred and fifty HCV4a patients, 224 HCV4a-HCC patients, and 84 healthy controls were enrolled in the study. Expression levels of miR214-5p, miR-125b, miR-1269 and miR-375 were quantified using quantitative real-time PCR.

RESULTS

Expression of the selected miRNAs in serum was significantly lower in HCC patients than in the healthy controls, except for miR-1269 and miR-494. There was a significant difference between HCC and HCV patients, in particular for HCC and late stage fibrosis, rather than HCV patients and early fibrosis. It is obvious that miR-1269 was significantly upregulated in HCC cases compared to hepatic fibrosis cases. Each miRNA can show HCC progression. Multivariate logistic regression analysis indicated that the tested panel of miRNAs (miR214-5p, miR-125b, miR-1269 and miR-375) represent accurate and specific indictors of HCC development.

CONCLUSION

This study presents a panel of miRNAs with strong power as putative diagnostic and prognostic biomarkers for HCV-induced HCC. Moreover, miR-214-5p and miR-1269 could be considered as early biomarkers for tracking the progress of liver fibrosis to HCC.

Keywords: MicroRNA, Hepatocellular carcinoma, Fibrosis progression

Core tip: Lack of compelling methods for early diagnosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) disease leads to poor prognosis. The identification of more reliable markers for diagnosis of HCC with easy methodologies for HCC screening and detection in early stage is desperately required. A collection of small non-coding circulating RNAs associated with HCC related-HCV has been found to be differentially communicated and included in the pathogenesis of the disease. Thus, we can use these molecules as prospective biomarkers for HCC, with some of the miRNAs representing biomarkers for liver fibrosis progression.