Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2021; 13(11): 1753-1765
Published online Nov 27, 2021. doi: 10.4254/wjh.v13.i11.1753
Circulating microRNA 9-3p and serum endocan as potential biomarkers for hepatitis C virus-related hepatocellular carcinoma
Amany Mohamed Salah Eldin Wahb, Mohamed El Kassas, Ahmed Kamal Khamis, Mostafa Elhelbawy, Nesreen Elhelbawy, Mona Salah Eldin Habieb
Amany Mohamed Salah Eldin Wahb, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
Mohamed El Kassas, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
Ahmed Kamal Khamis, Mostafa Elhelbawy, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom 32512, Menoufia, Egypt
Nesreen Elhelbawy, Mona Salah Eldin Habieb, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin Elkoum 3511, Egypt
Author contributions: Wahb A designed the research; Wahb A and Habieb M performed the laboratory work, performed the RT-qPCR work and drafted the manuscript; El Kassas M, Khamis A and Elhelbawy M performed the case selection and the clinical and radiological evaluations; Habieb M supplied reagents; Elhelbawy N performed the data analysis, biological parameter assessment and performed the RT-qPCR work; all authors contributed equally to the manuscript drafting and revision; All authors approved the final version of the manuscript.
Institutional review board statement: The study was approved by the Menoufia University Faculty of Medicine Research Ethics Committee.
Informed consent statement: Written informed consent was obtained from the patient or his/her guardians prior to the study.
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: No additional data are available.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article 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 NonCommercial (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:
Corresponding author: Mohamed El Kassas, MD, Associate Professor, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Ain Helwan, Cairo 11795,
Received: April 16, 2021
Peer-review started: April 16, 2021
First decision: June 23, 2021
Revised: July 2, 2021
Accepted: September 1, 2021
Article in press: September 1, 2021
Published online: November 27, 2021
Research background

The high mortality rate of hepatocellular carcinoma (HCC) in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection (HCV) and late diagnosis of the carcinoma.

Research motivation

MicroRNAs (miRNA), which regulate tumor proliferation and metastasis in HCC, may serve as a useful diagnostic approach for the early detection of HCC, thus decreasing its mortality. Meanwhile, endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes.

Research objectives

To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters.

Research methods

We compared levels of endocan and circulating miRNA 9-3p from 35 HCV-related HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls.

Research results

The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups, while levels in the chronic liver disease were significantly lower than those in the control group (P < 0.001). While the levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups. Moreover, miRNA 9-3p and endocan performed better than α-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients. The levels of miRNA 9-3p are significantly inversely correlated to vascular invasion (P = 0.002), stage of advancement of Barcelona Clinical Liver Cancer (P < 0.001 and the metastatic site (P < 0.001) of the HCC group.

Research conclusions

Endocan and miRNA 9-3p could be biomarkers with potential use for the early diagnosis of HCV-related HCC. In this regard, they are more valuable than α-fetoprotein. Moreover, miRNA 9-3p is an independent predictor of metastasis in HCC patients.

Research perspectives

The findings of this study warrant additional investigation in prospective trials with larger cohorts and longer follow-up for confirming our results and validating the potential clinical use of these markers in early HCC detection.