Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2020; 26(2): 168-183
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.168
Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 as serum innovative non-invasive biomarkers: Recent insights into Egyptian patients with hepatitis C virus type 4
Nourhan M El Samaloty, Marwa I Shabayek, Ramy S Ghait, Shohda A El-Maraghy, Sherine M Rizk, Maha M El-Sawalhi
Nourhan M El Samaloty, Marwa I Shabayek, Biochemistry Section, Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo 11795, Egypt
Ramy S Ghait, Internal Medicine, Gastroenterology and Hepatology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
Shohda A El-Maraghy, Sherine M Rizk, Maha M El-Sawalhi, Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
Author contributions: El-Sawalhi MM, Shabayek MI, El-Maraghy SA and Rizk SM conceived and designed the study; El Samaloty NM and Ghait RS performed the experiments; El Samaloty NM, Shabayek MI, El-Maraghy SA, Rizk SM and El-Sawalhi MM analyzed the data and wrote the paper; all authors have read and approve the final manuscript.
Institutional review board statement: This study was approved by the Research Ethics Committee for Experimental and Clinical studies at the Faculty of Pharmacy, Cairo University (approval number: BC 1955).
Informed consent statement: Written informed consents were obtained from all participants before being included in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE guidelines, and the manuscript was prepared and revised according to the STROBE guidelines.
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/
Corresponding author: Marwa I Shabayek, PhD, Assistant Professor, Associate Professor, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, 90th New Cairo Street, Cairo 11795, Egypt. marwa.ismail@fue.edu.eg
Received: October 8, 2019
Peer-review started: October 8, 2019
First decision: December 5, 2019
Revised: December 11, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: January 14, 2020
Processing time: 96 Days and 13.6 Hours
ARTICLE HIGHLIGHTS
Research Background

Hepatitis C virus (HCV) infection is a complex multifactorial process that involves multiple viral and host interactions. Besides, the high mutation rate of HCV that enables the virus to generate escape mutants resistant to treatment, emphasizing the need for a proper understanding of the pathogenesis of HCV infection, and various research efforts should be oriented to develop novel diagnostic and prognostic molecular tools.

Research motivation

lncRNAs are transcripts greater than 200 nucleotides with poor coding potential, that play important roles in regulating gene expression. Emerging evidence suggests that lncRNAs play relevant roles in viral infection and in antiviral responses. To date, the expression profiles of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 in HCV GT4 patients and their clinical relevance as biomarkers for HCV infection have not been studied yet.

Research objectives

To assess the serum levels of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 in naïve, treated and relapsed Egyptian HCV patients to examine their relation to HCV infection and their potential usefulness as new diagnostic and prognostic biomarkers for HCV GT4.

Research methods

Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction. The study included six groups; group I healthy controls and group II naïve HCV patients without treatment. Groups from III to V comprised HCV patients treated daily with three different 12-wk oral treatment regimens as follows: Group III received combination of sofosbuvir and simeprevir. Group IV received combination of sofosbuvir and daclatasvir. Group V received sofosbuvir and daclatasvir with ribavirin. Group VI included HCV patients who relapsed after 12-week treatment with sofosbuvir and simeprevir.

Research results

We found that serum levels of lncRNAGAS5 and LncRNABISPR were upregulated, whereas mRNA BST2 and LncRNA HEIH levels were downregulated in naïve patients compared to healthy controls. In contrast, HCV patients treated with sofosbuvir and simeprevir; with sofosbuvir and daclatasvir; or with sofosbuvir, daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients. Notably, patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients. Moreover, lncRNA GAS5, lncRNA BISPR and mRNA BST2 could differentiate naïve patients from controls and treated patients, whereas lncRNA HEIH best differentiated relapsed from treated patients.

Research conclusions

Differential expression of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 in naïve, treated and relapsed HCV Egyptian patients suggests their involvement in HCV-pathogenesis or antiviral response. In addition, lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 could serve as potential diagnostic biomarkers in HCV GT4 Egyptian patients while, lncRNA GAS5, lncRNA BISPR and mRNA BST2 could also be considered novel prognostic biomarkers for treatment in HCV patients. Importantly, lncRNA HEIH might represent a powerful prognostic marker for differentiating relapsed patients from sofosbuvir and simeprevir treatment.

Research perspectives

Further multicentre studies with large number of participants infected with either HCV or other infectious agents unlike HCV should be conducted to justify the specificity of these markers. Moreover, a prospective longitudinal study is needed to follow the same group of patients before and after treatment to confirm the potential of these biomarkers as prognostic tools for HCV and occurrence of relapse after therapy.