A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells

Ju Seog Lee, Jeonghoon Heo, Louis Libbrecht, In Sun Chu, Pal Kaposi-Novak, Diego F. Calvisi, Arsen Mikaelyan, Lewis R. Roberts, Anthony J. Demetris, Zongtang Sun, Frederik Nevens, Tania Roskams, Snorri S. Thorgeirsson

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697 Scopus citations

Abstract

The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development.

Original languageEnglish (US)
Pages (from-to)410-416
Number of pages7
JournalNature Medicine
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, J. S., Heo, J., Libbrecht, L., Chu, I. S., Kaposi-Novak, P., Calvisi, D. F., Mikaelyan, A., Roberts, L. R., Demetris, A. J., Sun, Z., Nevens, F., Roskams, T., & Thorgeirsson, S. S. (2006). A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nature Medicine, 12(4), 410-416. https://doi.org/10.1038/nm1377