A common genetic trait through multistep hepatocarcinogenesis in a case with chronic hepatitis C
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ABSTRACT:
PROVIDER: PRJNA643243 | ENA |
REPOSITORIES: ENA
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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:LEC rats are considered as interesting model for studying hepatitis and development of hepatocarcinogenesis related to copper accumulation and oxidative stress. LEC rats have a mutation in a gene related to liver copper excretion, the Atp7b gene. As a consequence, this rat strain shows an abnormal copper accumulation in the liver. This is believed to be the origin of the acute hepatitis and the subsequent hepatocellular carcinoma that spontaneously develop in these rats. Here, we present the gene expression profiles of LEC rats at different disease stages. LEC rats were classified as normal 6 weeks old (6w), normal 9 weeks old (9w), slight jaundice and jaundice according to age and disease state. D-penicillamine, a copper chelator agent, blocks both hepatitis and tumor development. D-penicillamine-trated LEC rats were used as control rats for gene expression comparison as they showed neither hepatitis development nor tumor marker expression. Gene expression differences in protein metabolism and tumor marker proteins add to the known oxidative stress and inflammation characterization of the hepatitis process, leading to new insights concerning hepatitis and hepatocarcinogenesis development. Keywords: disease state analysis
2008-04-25 | GSE7654 | GEO
Project description:LEC rats are considered as interesting model for studying hepatitis and development of hepatocarcinogenesis related to copper accumulation and oxidative stress. LEC rats have a mutation in a gene related to liver copper excretion, the Atp7b gene. As a consequence, this rat strain shows an abnormal copper accumulation in the liver. This is believed to be the origin of the acute hepatitis and the subsequent hepatocellular carcinoma that spontaneously develop in these rats. Here, we present the gene expression profiles of LEC rats at different disease stages. LEC rats were classified as normal 6 weeks old (6w), normal 9 weeks old (9w), slight jaundice and jaundice according to age and disease state. D-penicillamine, a copper chelator agent, blocks both hepatitis and tumor development. D-penicillamine-trated LEC rats were used as control rats for gene expression comparison as they showed neither hepatitis development nor tumor marker expression. Gene expression differences in protein metabolism and tumor marker proteins add to the known oxidative stress and inflammation characterization of the hepatitis process, leading to new insights concerning hepatitis and hepatocarcinogenesis development. Keywords: disease state analysis 6 weeks old LEC rats, 6 rats per group, were sacrified at different hepatitis stages. Biochemical and histological analyses were performed in order to classify the rats into normal, slight jaundice or jaundice groups. D-penicillamine-treated LEC rats (100 mg/kg/day p.o.) were used as control rats since they behave as normal rats. Microarray analysis was performed on liver samples, one replicate per rat, using dyes swap.
2008-04-24 | E-GEOD-7654 | biostudies-arrayexpress
Project description:BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) Tg mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis. METHODS: Three-month-old HBV Tg mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nonTg donors. Liver tissues were obtained every three months until 18 months at which time all mice developed multiple liver tumors. Nitrative DNA lesions and hepatocyte turnover were assessed immunohistochemically. Gene expression profiles were generated by extracting total RNA from the tissues and analyzing by microarray. RESULTS: The nitrative DNA lesions and the regenerative proliferation of hepatocytes were increased during the progression of chronic liver disease. In a gene expression profile analysis of liver samples, the chemokine- and T cell receptor (TCR)-mediated pathways were enhanced during chronic hepatitis, and the EGF- and VEGF-mediated pathways were induced in HCC. Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues. CONCLUSIONS: HBV-specific immune responses caused unique molecular signatures in the liver tissues of chronic hepatitis and triggered subsequent carcinogenic gene expression profiles in a mouse model. The results suggest a plausible molecular basis responsible for HBV-induced immune pathogenesis of HCC.
2017-08-29 | GSE103205 | GEO
Project description:Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. We performed spatial transcriptomics to investigate the intrahepatic cell heterogeneity and the spatial distribution of transcriptionally active HBV integration events in different phases of chronic HBV infection. Our analysis revealed that transcriptionally active HBV integration occurred in chronically HBV-infected patients in different phases, including those patients with HBsAg loss, and antiviral treatment was associated with a decreased number and extent of viral integrations.
2023-09-30 | GSE243367 | GEO
Project description:Hepatoarcinogenesis is a slow and multistep process. We used Hepatitis B virus X antigen (HBx) induced Hepatocellular carcinoma (HCC) as model. We also identify the biomarkers, the pathways and networks underlying HCC formation in this animal model. We analyzed the events from the early, middle, and late stages, in order to predict and prevent the development of cancer. At each specific stage, we analyzed the expression level that differed at least two-fold between HBx transgenic and wild-type mouse liver. Statistical approaches were used to identify genes displaying an increasing or decreasing trend throughout hepatocarcinogenesis.
2010-09-16 | GSE15251 | GEO
Project description:Adaptive laboratory evolution is highly effective for improving desired traits through natural selection. However, its applicability is inherently constrained to growth-correlated traits precluding traits of interest that incur a fitness cost, such as metabolite secretion. Here, we introduce the concept of tacking trait enabling natural selection of fitness-costly metabolic traits. The concept is inspired from the tacking maneuver used in sailing for traversing upwind. We use first-principle metabolic models to design an evolution niche wherein the tacking trait and fitness become correlated. Adaptive evolution in this niche, when followed by the reversal to the original niche, manifests in the improvement of the desired trait due to biochemical coupling between the tacking and the desired trait. We experimentally demonstrate this strategy, termed EvolveX, by evolving wine yeasts for increased aroma production. Our results pave the way for precision laboratory evolution for biotechnological and ecological applications.
2022-07-12 | PXD023171 | Pride
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC. 156 primary tissues and 25 cultured normal and HCC cell lines
2014-09-16 | E-GEOD-60753 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC.
2014-09-16 | GSE60753 | GEO
Project description:Hepatoarcinogenesis is a slow and multistep process. We used Hepatitis B virus X antigen (HBx) induced Hepatocellular carcinoma (HCC) as model. We also identify the biomarkers, the pathways and networks underlying HCC formation in this animal model. We analyzed the events from the early, middle, and late stages, in order to predict and prevent the development of cancer. At each specific stage, we analyzed the expression level that differed at least two-fold between HBx transgenic and wild-type mouse liver. Statistical approaches were used to identify genes displaying an increasing or decreasing trend throughout hepatocarcinogenesis. The liver was excised from 6-week-, 8-month-, 12-month-, 14-month-, and 16-month-old HBx transgenic mice (A106 strain) and RNA samples were isolated. In both 14-month- and 16-month-old mice, samples were obtained from both the tumor tissue and the normal.
2010-09-16 | E-GEOD-15251 | biostudies-arrayexpress