title: Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.
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.
authors.affiliation: Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Ja June
authors.initials: JJ
authors.lastname: Jang
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Yi
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.forename: Kuhn Uk
authors.initials: KU
authors.lastname: Lee
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Park
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
mesh_terms: 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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