Nature Medicine
- 12, 410 - 416 (2006)
Published online: 12 March 2006; | doi:10.1038/nm1377
A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cellsJu-Seog Lee1, Jeonghoon Heo1, Louis Libbrecht2, In-Sun Chu3, Pal Kaposi-Novak1, Diego F Calvisi1, Arsen Mikaelyan1, Lewis R Roberts4, Anthony J Demetris5, Zongtang Sun6, Frederik Nevens2, Tania Roskams2 & Snorri S Thorgeirsson11
Lab of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 4146, Bethesda, Maryland 20892, USA. 2
Departments of Morphology and Molecular Pathology, University of Leuven, Minderbroedersstraat 12, B-3000 Leuven, Belgium. 3
National Genome Information Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-dong, Yuseong-gu, Taejun, 305-333, Korea. 4
Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. 5
Thomas E. Starzl Transplant Institute, University of Pittsburgh Medical Center, UPMC Montefiore E-741, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA. 6
National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, P.O. Box 2258, Beijing 100021, China.
Correspondence should be addressed to Snorri S Thorgeirsson snorri_thorgeirsson@nih.gov 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.
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