Exp Mol Med.  2018 Jan;50(1):e419. 10.1038/emm.2017.164.

In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment

Affiliations
  • 1Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yujin.hoshida@mssm.edu
  • 2Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
  • 3Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4Division of Surgical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.

Abstract

Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations. Here we demonstrate that transcriptomic hepatocellular carcinoma subtypes, S1 and S2, determined by our previous transcriptome meta-analysis of multiple clinical hepatocellular carcinoma cohorts, are presented in a panel of hepatoma cell lines widely used by the research community. Interestingly, cell line that resembles gene expression pattern of S3 subtype, representing less aggressive tumors, was not identified in the panel. MYC pathway-activated S2-like cell lines showed higher sensitivity to a small molecule BET bromodomain inhibitor, (+)-JQ1, which has anti-MYC activity. These results support the use of hepatoma cell lines as models to evaluate molecular subtype-specific drug response, which is expected to lead to development of tailored, precision care of the patients with hepatocellular carcinoma.


MeSH Terms

Carcinoma, Hepatocellular*
Cell Line
Cohort Studies
Epigenomics
Gene Expression
Humans
In Vitro Techniques*
Models, Theoretical
Population Characteristics
Transcriptome
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr