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World J Gastrointest Pathophysiol. Jan 22, 2022; 13(1): 1-14
Published online Jan 22, 2022. doi: 10.4291/wjgp.v13.i1.1
Molecular and genetic markers in hepatocellular carcinoma: In silico analysis to clinical validation (current limitations and future promises)
Sarah El-Nakeep
Sarah El-Nakeep, Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
Author contributions: El-Nakeep S wrote the manuscript, collected the data, and draw the figures using powerpoint.
Conflict-of-interest statement: Sarah El-Nakeep declares that she has no conflict of interest.
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: https://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: March 21, 2021
Peer-review started: March 21, 2021
First decision: May 1, 2021
Revised: May 15, 2021
Accepted: December 22, 2021
Article in press: December 22, 2021
Published online: January 22, 2022
Abstract

Hepatocellular carcinoma (HCC) is the second cause of cancer-related mortality. The diagnosis of HCC depends mainly on α-fetoprotein, which is limited in its diagnostic and screening capabilities. There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment. New targets of therapy could enhance survival and create future alternative curative methods. In silico analysis provides both; discovery of biomarkers, and understanding of the molecular pathways, to pave the way for treatment development. This review discusses the role of in silico analysis in the discovery of biomarkers, molecular pathways, and the role the author has contributed to this area of research. It also discusses future aspirations and current limitations. A literature review was conducted on the topic using various databases (PubMed, Science Direct, and Wiley Online Library), searching in various reviews, and editorials on the topic, with overviewing the author’s own published and unpublished work. This review discussed the steps of the validation process from in silico analysis to in vivo validation, to incorporation into clinical practice guidelines. In addition, reviewing the recent lines of research of bioinformatic studies related to HCC. In conclusion, the genetic, molecular and epigenetic markers discoveries are hot areas for HCC research. Bioinformatics will enhance our ability to accomplish this understanding in the near future. We face certain limitations that we need to overcome.

Keywords: Hepatocellular carcinoma, In silico analysis, Bioinformatics, Biomarkers, Molecular pathways, Genetics, Epigenetics

Core tip: Hepatocellular carcinoma (HCC) is the second cause of cancer-related mortality. The importance of having an early detecting biomarker is to allow for curative measures to be applicable, and prognostic biomarkers to detect survival, in dealing with the disease. In silico analyses allow us to discover new genetic and epigenetic biomarkers, along with establishing the coexpression patterns, which impact HCC survival. Also, it allows for understanding the molecular pathways for HCC pathogenesis, and the discovery of potential therapeutic options. In this article, I review the current discoveries and limitations that face researchers to reach their ultimate goal of establishing clinical practice guidelines. I give an overview of the future potential that could benefit integrated research on HCC and discuss my own research related to the topic.