Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.
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.
Woo
Hyun Goo
HG
Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Lee
Jeong-Hoon
JH
Yoon
Jung-Hwan
JH
Kim
Chung Yong
CY
Lee
Hyo-Suk
HS
Jang
Ja June
JJ
Yi
Nam-Joon
NJ
Suh
Kyung-Suk
KS
Lee
Kuhn Uk
KU
Park
Eun Sung
ES
Thorgeirsson
Snorri S
SS
Kim
Yoon Jun
YJ
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism*; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D013234:Stem Cells / Q000166:cytology
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