Genome-wide analysis of different response of the hepatocytes and oval cells induced by aflatoxin B1 exposure
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125745 | GEO | 2019/01/29
REPOSITORIES: GEO
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Project description:Analysis of genetic changes of hepatocytes and oval cells induced by HBV. The hypothesis tested in the present study was that hepatic progenitor cells (oval cells) are the founder cells of hepatocellular carcinoma (HCC). Results provide important information of the different responses of hepatocytes and oval cells to HBV expression during HBV-related hepatocarcinogenesis, such as up- or down-regulated oncogenes,tumor suppressor genes and signaling pathways.Results also provide new insights into the biology of human HCC. Total RNA obtained from primary cultured hepatocytes and oval cells isolated from the healthy and HBV transgenic mice.
2012-07-11 | E-GEOD-39289 | biostudies-arrayexpress
Project description:Analysis of genetic changes of hepatocytes and oval cells induced by HBV. The hypothesis tested in the present study was that hepatic progenitor cells (oval cells) are the founder cells of hepatocellular carcinoma (HCC). Results provide important information of the different responses of hepatocytes and oval cells to HBV expression during HBV-related hepatocarcinogenesis, such as up- or down-regulated oncogenes,tumor suppressor genes and signaling pathways.Results also provide new insights into the biology of human HCC.
2012-07-12 | GSE39289 | GEO
Project description:The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by mapping the entire liver of patients with HCC. We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes with intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center in individual livers of 11 patients with HCC and on selected LCM samples. HBV biomarkers were determined by real-time PCR and confocal immunofluorescence. Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HBsAg. The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipid and fatty acid, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARa/RXRa nuclear receptors, comprising PGC1 and FOXO1, two key regulators of the hepatic metabolic functions and HBV transcription. These findings were confirmed by gene expression of microdissected hepatocytes. However, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen (CTA) genes, NUF2 and TTK. HCC-associated with HBV is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets. Samples were obtained at various distances from the tumor center in individual livers of 11 patients with HBV-associated HCC. Whole liver tissue samples were compared to LCM samples of malignant and non-malignant hepatocytes obtained from the same livers. This dataset is part of the TransQST collection.
2014-12-22 | E-GEOD-55092 | biostudies-arrayexpress
Project description:Objective: Antigen-specific immunotherapy is a promising strategy to treat hepatitis B virus (HBV) infection and (HBV-related) hepatocellular carcinoma (HCC). To facilitate killing of malignant and/or infected hepatocytes, it is vital to know which T cell targets are presented by HLA-I complexes on patient-derived hepatocytes. Here, we aimed to reveal the hepatocyte-specific HLA-I peptidome with emphasis on peptides derived from HBV proteins and tumor associated antigens (TAAs) to guide development of antigen-specific immunotherapy. Design: Primary human hepatocytes were isolated with high purity from (HBV infected) non-tumor and HCC tissues using a newly designed perfusion-free procedure. Subsequently, hepatocyte-derived HLA-bound peptides were identified by mass spectrometry after which source proteins were subjected to gene ontology and pathway analysis. Finally, all HBV-antigen and TAA-derived HLA-peptides were extracted and a selection was tested for immunogenicity. Results: We acquired a high quality HLA-I peptidome of 2x105 peptides, of which source proteins were associated with hepatocyte function. Importantly, we demonstrated HLA-I presentation of HBV-derived and TAA-derived peptides for the first time in immune cell-depleted primary liver cell isolates. The peptidome included 8 HBV-derived peptides and 14 peptides from 8 known HCC-associated TAAs that were exclusively identified in tumor eluates. Of these, immunogenicity was demonstrated for 5 HBV-derived and 3 TAA-derived peptides. Conclusion: We present a first HLA-I immunopeptidome of isolated primary human hepatocytes, devoid of immune cells. Our results directly aid development of antigen-specific immunotherapy for HBV infection and HCC. Described methodology can also be applied to personalize immunotherapeutic treatment of liver diseases in the future.
2022-09-05 | PXD023143 | Pride
Project description:The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by mapping the entire liver of patients with HCC. We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes with intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center in individual livers of 11 patients with HCC and on selected LCM samples. HBV biomarkers were determined by real-time PCR and confocal immunofluorescence. Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HBsAg. The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipid and fatty acid, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARa/RXRa nuclear receptors, comprising PGC1 and FOXO1, two key regulators of the hepatic metabolic functions and HBV transcription. These findings were confirmed by gene expression of microdissected hepatocytes. However, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen (CTA) genes, NUF2 and TTK. HCC-associated with HBV is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets.
2014-12-22 | GSE55092 | GEO
Project description:Common genetic traits are not well defined in hepatocellular carcinoma (HCC), because necroinflammation lasting long in prior to hepatocarcinogenesis embeds highly heterogenous genetic background in hepatocytes over the liver. We experienced a rare case with chronic hepatitis C, in which multiple liver tumors at different stages in multistep hepatocarcinogenesis were observed at the same time. Under the same genetic and etiological backgrounds, comparisons of expression profiles among dysplastic nodules (DN), well differentiated HCC (WEL), and moderately differentiated HCC (MOD) would provide critical genetic information for the initiation and progression of HCC.
2020-07-24 | GSE153565 | GEO
Project description:Genome-wide analysis of different response of hepatocytes and oval cells to hepatitis B virus expression during HBV-related hepatocarcinogenesis
| PRJNA170482 | ENA
Project description:Comparison of gene expression profiles induced by the mycotoxin, aflatoxin B1 (AFB1), in primary human hepatocytes and HepaRG cells. Initial mechanisms involved in the complex multistep process leading to malignant transformation by chemicals remain largely unknown. We have analysed changes in gene expression profiles in primary human hepatocytes and differentiated human hepatoma HepaRG cells after a 24 h treatment with 0.05 or 0.25µM aflatoxin B1 (AFB1), a potent genotoxic hepatocarcinogen. Three independent biological replicates of HepaRG cell cultures and two pools of three primary human hepatocyte cultures each, were investigated. Cells were treated with 0.05 or 0.25µM AFB1 for 24 h.
2010-12-07 | E-GEOD-25844 | biostudies-arrayexpress
Project description:Comparison of gene expression profiles induced by the mycotoxin, aflatoxin B1 (AFB1), in primary human hepatocytes and HepaRG cells. Initial mechanisms involved in the complex multistep process leading to malignant transformation by chemicals remain largely unknown. We have analysed changes in gene expression profiles in primary human hepatocytes and differentiated human hepatoma HepaRG cells after a 24 h treatment with 0.05 or 0.25µM aflatoxin B1 (AFB1), a potent genotoxic hepatocarcinogen.
2010-12-07 | GSE25844 | GEO
Project description:<p>Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). In this study we sequenced the whole genome (~80X) and transcriptome of tumor and non-tumor samples from four HCC patients and identified over two hundred HBV integration sites. We found significant clonal expansion of HBV-integrated hepatocytes specifically in the tumor samples. We observed a diverse collection of genomic perturbations near viral integration sites, including gene disruption, viral promoter-driven human transcription, viral-human transcript fusion and DNA copy number alteration. We also sequenced one patient at ultra-high coverage (~240X) to build the most comprehensive HBV-integration landscape yet attempted. Our data suggest that the viral integration significantly expands carcinogenic opportunities in HBV-infected individuals.</p>
| phs000384 | dbGaP