Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2018; 24(35): 3974-3979
Published online Sep 21, 2018. doi: 10.3748/wjg.v24.i35.3974
Biomarkers for hepatocellular carcinoma: What’s new on the horizon?
Matthias Ocker
Matthias Ocker, Department of Translational Medicine Oncology, Bayer AG, Berlin 13353, Germany
Matthias Ocker, Charité University Medicine Berlin, Berlin 10117, Germany
Author contributions: Ocker M solely contributed to the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
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/
Correspondence to: Matthias Ocker, MD, Professor, Department of Translational Medicine Oncology, Bayer AG, Muellerstrasse 178, Berlin 13353, Germany. matthias.ocker@bayer.com
Telephone: +49-30-468194799 Fax: +49-30-468994799
Received: June 11, 2018
Peer-review started: June 12, 2018
First decision: July 6, 2018
Revised: July 29, 2018
Accepted: August 1, 2018
Article in press: August 1, 2018
Published online: September 21, 2018

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids (DNA, RNA or miRNA-containing exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

Keywords: Hepatocellular carcinoma, Biomarker, Next-generation sequencing, Liquid Biopsy, Functional imaging, Molecular imaging, Circulating free DNA, Circulating tumor cells, Immune checkpoint inhibitors

Core tip: Hepatocellular carcinoma (HCC) is a heterogeneous disease with various underlying etiologies and an overall still poor prognosis. Biomarkers to identify optimal treatment for distinct patients are still lacking for HCC due to limited availability of biopsies. Novel treatment options, esp. immune checkpoint inhibitors, may need novel biomarker approaches and non-tissue based technologies might provide a solution to identify those biomarkers. In this article, the current status of biomarker identification for HCC is discussed.