A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.
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.
Lab of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 4146, Bethesda, Maryland 20892, USA.
Ju-Seog
JS
Lee
Jeonghoon
J
Heo
Louis
L
Libbrecht
In-Sun
IS
Chu
Pal
P
Kaposi-Novak
Diego F
DF
Calvisi
Arsen
A
Mikaelyan
Lewis R
LR
Roberts
Anthony J
AJ
Demetris
Zongtang
Z
Sun
Frederik
F
Nevens
Tania
T
Roskams
Snorri S
SS
Thorgeirsson
D000368:Aged; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002681:China / Q000208:ethnology; D016000:Cluster Analysis; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D051381:Rats; D015203:Reproducibility of Results; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D016019:Survival Analysis; D044465:White People
D004273:DNA, Neoplasm