Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.
Cancer Res, 2010/4/15;70(8):3034-41.
Woo HG[1], Lee JH, Yoon JH, Kim CY, Lee HS, Jang JJ, Yi NJ, Suh KS, Lee KU, Park ES, Thorgeirsson SS, Kim YJ
Affiliations
PMID: 20395200DOI: 10.1158/0008-5472.CAN-09-2823
Impact factor: 13.312
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapping phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). Similar to CC and CHC, CLHCC showed an aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell-like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that the prognostic value of the CC signatures was independent of the expression of those signatures. In conclusion, we suggest that the acquisition of cholangiocarcinoma-like expression traits plays a critical role in the heterogeneous progression of HCC.
MeSH terms
Carcinoma, Hepatocellular; Cell Proliferation; Cholangiocarcinoma; Disease-Free Survival; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Liver Neoplasms; Oligonucleotide Array Sequence Analysis; Phenotype; Prognosis; Prospective Studies; Stem Cells
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