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
Abstract
BACKGROUND

Hepatitis C virus (HCV) infection and its consequent complications are undeniably a public health burden worldwide, particularly in Egypt. Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.

AIM

To investigate the expression profiles of circulating lncRNAGAS5, lncRNAHEIH, lncRNABISPR and mRNABST2 in naïve, treated and relapsed HCV Egyptian patients, to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.

METHODS

One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study. Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated, whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients. 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. LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P < 0.001, whereas mRNABST2 was negatively correlated with viral load at P < 0.001 and ALT at P < 0.05. Interestingly, a significant positive correlation between lncRNA HEIH and AFP was observed at P < 0.001.

CONCLUSION

Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.

Keywords: lncRNA GAS5, lncRNA BISPR, mRNA BST2, lncRNA HEIH, Hepatitis C, Biomarkers

Core tip: The expression profiles of the studied RNAs in naïve, treated and relapsed hepatitis C virus (HCV) Egyptian patients suggest their involvement in HCV-pathogenesis or antiviral response. Additionally, 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 SOF + SIM treatment. Finally, these biomarkers can be used in combination to complete the whole picture of diagnosis, prognosis and follow-up of HCV.