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A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition.

Authors
 Jae Yeon Seok  ;  Deuk Chae Na  ;  Hyun Goo Woo  ;  Massimo Roncalli  ;  So Mee Kwon  ;  Jeong Eun Yoo  ;  Ei Yong Ahn  ;  Gwang Il Kim  ;  Jin-Sub Choi  ;  Young Bae Kim  ;  Young Nyun Park 
Citation
 HEPATOLOGY, Vol.55(6) : 1776-1786, 2012 
Journal Title
 HEPATOLOGY 
ISSN
 0270-9139 
Issue Date
2012
MeSH
Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms/genetics* ; Bile Duct Neoplasms/mortality ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic* ; Carcinoma, Hepatocellular/mortality ; Carcinoma, Hepatocellular/pathology* ; Cholangiocarcinoma/genetics* ; Cholangiocarcinoma/mortality ; Cholangiocarcinoma/pathology ; Epithelial-Mesenchymal Transition* ; Female ; Fibrosis ; Gene Expression Profiling ; Humans ; Liver Neoplasms/mortality ; Liver Neoplasms/pathology* ; Male ; Middle Aged ; Signal Transduction ; Transforming Growth Factor beta/physiology
Keywords
Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms/genetics* ; Bile Duct Neoplasms/mortality ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic* ; Carcinoma, Hepatocellular/mortality ; Carcinoma, Hepatocellular/pathology* ; Cholangiocarcinoma/genetics* ; Cholangiocarcinoma/mortality ; Cholangiocarcinoma/pathology ; Epithelial-Mesenchymal Transition* ; Female ; Fibrosis ; Gene Expression Profiling ; Humans ; Liver Neoplasms/mortality ; Liver Neoplasms/pathology* ; Male ; Middle Aged ; Signal Transduction ; Transforming Growth Factor beta/physiology
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell-like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell-like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC. (HEPATOLOGY 2012;55:1776-1786).
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/hep.25570/abstract
DOI
22234953
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Gwang Il(김광일)
Na, Deuk Chae(나득채)
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Seok, Jae Yeon(석재연)
Ahn, Ei Yong(안의용)
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Choi, Jin Sub(최진섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90360
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