Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2021; 13(12): 2137-2149
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2137
New stem cell autophagy surrogate diagnostic biomarkers in early-stage hepatocellular carcinoma in Egypt: A pilot study
Tarek Yosef, Wesam Ahmed Ibrahim, Marwa Matboli, Amina Ahmed Swilam, Sarah El-Nakeep
Tarek Yosef, Wesam Ahmed Ibrahim, Sarah El-Nakeep, Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
Marwa Matboli, Department of Biochemistry, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
Amina Ahmed Swilam, Department of Internal Medicine, Health Affair Directorate, Ministry of Health and Population, Cairo 11591, Egypt
Author contributions: Yosef T supervised the conduction of the study; Ibrahim WA and El-Nakeep S followed the clinical collection of data and the availability of patients; El-Nakeep S and Matboli M formulated the research question and its applicability and wrote the final draft; Matboli M conducted the laboratory analysis; Swilam AA collected the data from the patients; all authors revised and accepted the final submitted manuscript.
Institutional review board statement: The Internal Medicine Department, Faculty of Medicine, Ain Shams University, approved this study’s protocol in 2016 for ethics of conducting the study and in accordance with the ethical standards of the Declaration of Helsinki. Informed consent was obtained from each participant. Both the patients and controls were randomly selected.
Informed consent statement: Informed consent was obtained from each participant. Both the patients and controls were randomly selected.
Conflict-of-interest statement: All Authors declare that they have no conflict of interest.
Data sharing statement: Data sharing of the original excel sheets and other datasets could be obtained upon request and approval of all authors.
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: Sarah El-Nakeep, MD, Associate Professor, Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Ramsees Street, Cairo 11591, Egypt. sarahnakeep@gmail.com
Received: May 4, 2021
Peer-review started: May 4, 2021
First decision: June 16, 2021
Revised: June 21, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: December 27, 2021
Research background

Autophagy is one of the pathways affected in hepatocellular carcinoma (HCC). Genetic regulation of this pathway through the SQSTM1 gene was established. Autophagy is responsible for the destruction of cellular components through lysosomal degradation. This process is responsible for cellular recycling and preservation. It protects from cancerous transformation, thus any imbalance in this mechanism will increase the risk of cancer.

Research motivation

We aimed to establish the genetic-epigenetic-phenotypic pathway related to the autophagic process in the pathogenesis of HCC and whether these studied biomarkers could be used as surrogate diagnostic markers for autophagy pathway in HCC.

Research objectives

We examined hsa-miR-519d microRNA effect on HCC and its association with the SQSTM1 genetic marker. We also examined the sensitivity and specificity of those biomarkers in the diagnosis of early-stage HCC cases.

Research methods

This is an observational study. We evaluated the candidate biomarkers through bioinformatics, and after establishing a computational statistical relation, we proceeded with their clinical association through laboratory validation. We measured the genetic and epigenetic biomarkers in the serum samples taken from HCC patients, chronic liver disease patients, and healthy participants. We used reverse transcription-polymerase chain reaction and quantitative reverse transcription-polymerase chain reaction.

Research results

We determined the sensitivity and specificity of each biomarker separately and combined as compared to the established alpha-fetoprotein (AFP) biomarker. We found that all the studied biomarkers in our study have better sensitivity and specificity than AFP, when used separately or combined, at the diagnosis of early-stage HCC.

Research conclusions

We could use the autophagy pathway biomarkers in the early-stage HCC diagnosis.

Research perspectives

More autophagy biomarkers could be examined using first in silico analysis then clinical laboratory confirmation. Combining computational and clinical validations in clinical studies could benefit the research process immensely.