Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma

Hyun Goo Woo, Jeong-Hoon Lee, Jung-Hwan Yoon, Chung Yong Kim, Hyo Suk Lee, Ja June Jang, Nam Joon Lee, Kyungsuk Suh, Kuhn Uk Lee, Eun Sung Park, Snorri S. Thorgeirsson, Yoon Jun Kim

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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.

Original languageEnglish
Pages (from-to)3034-3041
Number of pages8
JournalCancer Research
Volume70
Issue number8
DOIs
StatePublished - 15 Apr 2010

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Cholangiocarcinoma
Hepatocellular Carcinoma
Gene Expression
Phenotype
Gene Expression Profiling
Embryonic Stem Cells

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Woo, Hyun Goo ; Lee, Jeong-Hoon ; Yoon, Jung-Hwan ; Kim, Chung Yong ; Lee, Hyo Suk ; Jang, Ja June ; Lee, Nam Joon ; Suh, Kyungsuk ; Lee, Kuhn Uk ; Park, Eun Sung ; Thorgeirsson, Snorri S. ; Kim, Yoon Jun. / Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. In: Cancer Research. 2010 ; Vol. 70, No. 8. pp. 3034-3041.
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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.",
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Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. / Woo, Hyun Goo; Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Chung Yong; Lee, Hyo Suk; Jang, Ja June; Lee, Nam Joon; Suh, Kyungsuk; Lee, Kuhn Uk; Park, Eun Sung; Thorgeirsson, Snorri S.; Kim, Yoon Jun.

In: Cancer Research, Vol. 70, No. 8, 15.04.2010, p. 3034-3041.

Research output: Contribution to journalArticle

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AU - Jang, Ja June

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AU - Kim, Yoon Jun

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