Wahb AMSE, El Kassas M, Khamis AK, Elhelbawy M, Elhelbawy N, Habieb MSE. Circulating microRNA 9-3p and serum endocan as potential biomarkers for hepatitis C virus-related hepatocellular carcinoma. World J Hepatol 2021; 13(11): 1753-1765 [PMID: 34904043 DOI: 10.4254/wjh.v13.i11.1753]
Corresponding Author of This Article
Mohamed El Kassas, MD, Associate Professor, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Ain Helwan, Cairo 11795, Egypt.m_elkassas@hq.helwan.edu.eg
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
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/
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohamed El Kassas, MD, Associate Professor, Department of Endemic Medicine, Faculty of Medicine, Helwan University, Ain Helwan, Cairo 11795, Egypt.m_elkassas@hq.helwan.edu.eg
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 Processing time: 221 Days and 12.6 Hours
Abstract
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. 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.
AIM
To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters.
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 recruited from inpatient and outpatient clinics of the National Liver Institute, Menoufia University, Egypt in the period from January to March 2021 in a case-control study. Serum samples from all groups were analyzed for HCV. Endocan was measured by enzyme-linked immunosorbent assays, and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR.
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). 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 were 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.
CONCLUSION
Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.
Core Tip: The level of circulating microRNA 9-3p was significantly decreased in hepatocellular carcinoma (HCC) patients than in chronic liver disease and control groups. The level of serum endocan was significantly increased in HCC patients than in the cirrhotic and control groups, and there was better diagnostic performance of microRNA 9-3p and endocan than α-fetoprotein. The levels of microRNA 9-3p have a significant inverse correlation with endocan and vascular invasion and advanced stage of Barcelona Clinical Liver Cancer in the HCC group. Circulating microRNA 9-3p and endocan could be novel biomarkers for early diagnosis of hepatitis C virus-related HCC patients.
