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Identification of cholangiocarcinoma-like gene expression traits in hepatocellular carcinoma

ABSTRACT: We performed gene expression profiling of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and mixed type of combined HCC and CC (CHC). In comparison of the profiles, a novel class of HCC expressing CC-like traits was identified.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15765 | GEO | 2010/05/21

SECONDARY ACCESSION(S): PRJNA116801

REPOSITORIES: GEO

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Identification of cholangiocarcinoma-like gene expression traits in hepatocellular carcinoma

Project description:We performed gene expression profiling of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and mixed type of combined HCC and CC (CHC). In comparison of the profiles, a novel class of HCC expressing CC-like traits was identified. Gene expression profiling of 70 hepatocellular carcinoma (HCC), 13 cholangiocarcinoma (CC), and 7 mixed type of combined HCC and CC (CHC) were performed.

2010-06-09 | E-GEOD-15765 | biostudies-arrayexpress

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Project description:The study of human liver cancer has been hampered by the lack of reliable models that faithfully recapitulate the physiopathology of the patient’s original tumour ex vivo. Here, we describe the first culture system to allow the establishment and long-term expansion of human primary liver cancer (PLC) organoids (called tumoroids) from the three most common PLC subtypes: Hepatocellular carcinoma (HCC), Cholangiocarcinoma (CC) and mixed HCC/CC tumours (CHC). We evaluated whether tumoroid lines maintain the expression profile and the genomic landscape of the original tumor they derived from by performing genome-wide (RNAseq/WES) analyses before and after culture. These analyses reveal that the cultures closely recapitulate the gene expression and the mutational landscape of the original tumor, allowing discrimination between different tumor subtypes (HCC, CHC, CC).

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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 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

2012-08-31 | GSE31370 | GEO

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Mixed hepatocellular – cholangiocarcinoma derives from liver progenitor cells and depends on senescence and IL6 trans-signaling, single-cell RNA sequencing

2023-11-15 | GSE202089 | GEO

Primary Tumor-Derived Liver Cancer Organoids Promote Metastasis in vivo

Project description:Past studies have identified hepatic tumors with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) characteristics which have a more aggressive behavior and a poorer prognosis than classic HCC. Whether this pathological heterogeneity is due to a cell of origin of bipotent liver progenitors or the plasticity of cellular constituents comprising these tumors remains debated. In this study, we investigated the potential acquisition of CC-like traits during advanced development of HCC in mice. We first characterized the primary and rare high-grade HCC developed in a genetic mouse model. We further developed a mouse model of highly efficient HCC invasion and metastasis via orthotopic transplantation of liver cancer organoids (LCOs) propagated from primary tumors in the genetic model. We found invasive/metastatic tumors developed in both models closely recapitulated advanced human HCC, and displayed a striking acquisition of CC-related pathological and molecular features which was absent in the primary HCC tumors. Our study directly demonstrates the pathological evolution of HCC during advanced tumor development, providing the first evidence that tumors with mixed HCC and CC features, or at least a subset of these tumors, represent a more advanced developmental stage of HCC. Lastly, we found LCO-generated high-grade tumors exhibited significantly increased extracellular vesicle (EV) secretion, suggesting that identifying tumor-specific EV proteins in plasma may be a promising tool for liver cancer detection.

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