Published online Sep 21, 2018. doi: 10.3748/wjg.v24.i35.3974
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
Processing time: 100 Days and 18.4 Hours
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.
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.