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

ABSTRACT: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. It has been shown the phenotypic overlap between HCC and CC, comprising continuous liver cancer spectrum. As a proof of concept, a recent study has demonstrated a genomic subtype of HCC expressing CC-like gene expression trait, i.e. CC-like HCC, which has revealed common genomic trait of stem cell-like property and aggressive clinical outcome. However, the histopathological characteristics of these intermediate phenotype was not fully evaluated yet. Here, we found that a variant HCC with fibrous stromal component, i.e. scirrhous HCC, has CC-like genomic features. By performing gene expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of scirrhous HCC with CC and classical HCC. We found that the scirrhous HCC express both CC-like and stem cell-like expression traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of scirrhous HCC. Over-expression of transforming growth factor β (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of scirrhous HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression trait in HCC. The expression of stem cell-like trait and TGF-β/EMT molecules may play pivotal roles in the aggressive phenotype of scirrhous HCC

ORGANISM(S): Homo sapiens

PROVIDER: GSE31370 | GEO | 2012/08/31

SECONDARY ACCESSION(S): PRJNA145895

REPOSITORIES: GEO

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

Project description:Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. It has been shown the phenotypic overlap between HCC and CC, comprising continuous liver cancer spectrum. As a proof of concept, a recent study has demonstrated a genomic subtype of HCC expressing CC-like gene expression trait, i.e. CC-like HCC, which has revealed common genomic trait of stem cell-like property and aggressive clinical outcome. However, the histopathological characteristics of these intermediate phenotype was not fully evaluated yet. Here, we found that a variant HCC with fibrous stromal component, i.e. scirrhous HCC, has CC-like genomic features. By performing gene expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of scirrhous HCC with CC and classical HCC. We found that the scirrhous HCC express both CC-like and stem cell-like expression traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of scirrhous HCC. Over-expression of transforming growth factor Î² (TGF-Î²) signaling was also found, implying its regulatory role in the pathobiology of scirrhous HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression trait in HCC. The expression of stem cell-like trait and TGF-Î²/EMT molecules may play pivotal roles in the aggressive phenotype of scirrhous HCC Gene expression profiles of HCC, CC and HCC with fibrous stroma were compared.

2012-08-31 | E-GEOD-31370 | biostudies-arrayexpress

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Project description:Primary liver tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and a group of rare tumours exhibiting biliary and hepatocytic differentiation called combined hepatocholangiocarcinomas (cHCC-CC). To better define this latter group, we take advantage of a series of these tumours based on their morphological characteristics and we performed transcriptional analysis allowing thereafter global comparison with published data. We show that most cHCC-CCs express progenitor cell traits, are committed to biliary lineage and are mainly associated to the activation of Wnt/beta-catenin and TGFbeta signalling pathways. Wnt/beta-catenin pathway activation in cHCC-CC is evidenced by the expression of both its direct targets such as LEF1 and EPCAM. In addition, extracellular matrix (ECM) genes and ECM-remodelling genes which are upon the control of TGF profibrotic program were found up-regulated in cHCC-CC. Interestingly, we show that CC and most cHCC-CC share characteristics associated to a subtype of poorly differentiated HCC suggesting that these tumours could originate from a stem/progenitor cell. The plasticity of these cells may explain the phenotypical heterogeneity of these tumors with the maintenance of some hepatocellular differentiation features such as albumin expression. Interestingly, this is shared by at least one third of CC, raising the hypothesis of a potential continuum between CC, cHCC-CC and poorly differentiated HCC. Patients serie include 3 intra-hepatic CC, 7 typical HCC and 20 cHCC-CC that was used for microarray hybridisation. All these tumours did not show any mutation of the beta-catenin gene. The degree of hepatic fibrosis of the non-cancerous liver was graded according to the METAVIR classification. Paraffin sections were processed as described previously. Immunohistochemistry was done on standard slides for the series.

2012-03-31 | E-GEOD-35306 | biostudies-arrayexpress

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Genome-wide identification of transcripts associated with lncRNA-ATB by RIP-seq

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2019-06-20 | GSE133037 | GEO

Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFbeta signaling pathways

2012-04-01 | GSE35306 | GEO

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