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

Authors
Seok, JY; Na, DC; Woo, HG; Roncalli, M; Kwon, SM; Yoo, JE; Ahn, EY; Kim, GI; Choi, JS; Kim, YB; Park, YN
Citation
Hepatology (Baltimore, Md.), 55(6):1776-1786, 2012
Journal Title
Hepatology (Baltimore, Md.)
ISSN
0270-91391527-3350
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).
MeSH terms
AdultAgedAged, 80 and overBile Duct Neoplasms/*genetics/mortality/pathology*Bile Ducts, IntrahepaticCarcinoma, Hepatocellular/mortality/*pathologyCholangiocarcinoma/*genetics/mortality/pathology*Epithelial-Mesenchymal TransitionFemaleFibrosisGene Expression ProfilingHumansLiver Neoplasms/mortality/*pathologyMaleMiddle AgedSignal TransductionTransforming Growth Factor beta/physiology
DOI
10.1002/hep.25570
PMID
22234953
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
AJOU Authors
우, 현구김, 영배
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