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

Nat Med. 2006 Apr;12(4):410-6. doi: 10.1038/nm1377. Epub 2006 Mar 12.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / classification
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation
  • China / ethnology
  • Cluster Analysis
  • Cohort Studies
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • European Continental Ancestry Group
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Hepatocytes / cytology*
  • Hepatocytes / physiology
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / classification
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Rats
  • Reproducibility of Results
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Survival Analysis

Substances

  • DNA, Neoplasm

Associated data

  • GEO/GPL1528
  • GEO/GPL1529
  • GEO/GSE1897
  • GEO/GSE1898
  • GEO/GSE4024