Expression data from paired human primary HCC tissues and adjacent non-cancerous liver tissues.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166163 | GEO | 2021/02/12
REPOSITORIES: GEO
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Project description:Aim: Hepatic fibrosis is a major worldwide medical problem and can develop into liver cirrhosis and hepatocellular carcinoma(HCC). Until now, there are no effective drugs for liver ?brosis because the molecular mechanism of progression of liver fibrosis is not fully understood. MicroRNAs (miRNAs) are an important class of small non-coding functional RNAs that play a key role in many biological processes. The purpose of this study was to clarify how the aberrant expression of miRNAs participates in development of the liver fibrosis in rat liver fibrosis model. Methods: Fibrotic and paired normal liver tissues were collected and assesssed by deep sequencing technology. MiRNA pro?ling results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics was used to predict miRNA targets. Results: Nine deregulated miRNAs were induced in porcine serum (PS)-induced hepatic fibrosis versus normal liver. Further analysis revealed several signaling pathways (e.g., gap junction and neuroactive ligand-receptor interaction) may be associated with hepatic fibrogenesis. Conclusion: Several miRNAs are dysregulated in PS-induced hepatic fibrosis and seem to be closely associated with hepatic fibrogenesis. These results provide an experimental basis for understanding the mechanism of hepatic fibrosis. We sequenced two samples, including case and control. Each sample has two replicates.
2015-06-04 | E-GEOD-54028 | biostudies-arrayexpress
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2015-09-29 | GSE73498 | GEO
Project description:Aim: Hepatic fibrosis is a major worldwide medical problem and can develop into liver cirrhosis and hepatocellular carcinoma(HCC). Until now, there are no effective drugs for liver fibrosis because the molecular mechanism of progression of liver fibrosis is not fully understood. MicroRNAs (miRNAs) are an important class of small non-coding functional RNAs that play a key role in many biological processes. The purpose of this study was to clarify how the aberrant expression of miRNAs participates in development of the liver fibrosis in rat liver fibrosis model. Methods: Fibrotic and paired normal liver tissues were collected and assesssed by deep sequencing technology. MiRNA profiling results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics was used to predict miRNA targets. Results: Nine deregulated miRNAs were induced in porcine serum (PS)-induced hepatic fibrosis versus normal liver. Further analysis revealed several signaling pathways (e.g., gap junction and neuroactive ligand-receptor interaction) may be associated with hepatic fibrogenesis. Conclusion: Several miRNAs are dysregulated in PS-induced hepatic fibrosis and seem to be closely associated with hepatic fibrogenesis. These results provide an experimental basis for understanding the mechanism of hepatic fibrosis.
2015-06-04 | GSE54028 | GEO
Project description:Chronic hepatitis C virus (HCV) infection and cirrhosis are major risk factors for developing hepatocellular carcinoma (HCC). Genetic polymorphisms in the IFNL3/IFNL4 locus have been associated both with poor clearance of HCV and protection from liver fibrosis, an early stage of cirrhosis. Here, we aimed to address the genetic and functional relationships between IFNL3/IFNL4 polymorphisms, cirrhosis, and HCC risk. We evaluated associations between IFNL4 genotype (presence of rs368234815-dG or rs12979860-T alleles) with cirrhosis and HCC risk in patients with chronic HCV - 2,931 from Taiwan and 3,566 from Japan, and with gene expression and somatic mutations in 370 HCC tumors in The Cancer Genome Atlas (TCGA). Functional analyses were performed in primary human hepatocytes and hepatic stellate cells and a panel of hepatoma HepG2 cell lines with gene-edited IFNLR1 and inducible expression of IFN-λ3 or IFN-λ4. We detected associations between IFNL4 genotype and decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwan), but increased risk of HCC in patients without HCV clearance (OR=1.28, 95%CI=1.07-1.52, P=0.0058, in Japan). IFNL4 genotype was also associated with reduced cell proliferation and enrichment of CTNNB1 mutations in HCC tumors in TCGA. Reduced proliferation in hepatic cells was contributed by intracellular accumulation of IFN-λ4 leading to induction of ER stress and enhanced IRF1 signaling. The strong anti-proliferative effects of IFN-λ4 in hepatic cells could explain the association of IFNL3/IFNL4 polymorphisms with decreased cirrhosis. However, by sustaining persistent HCV infection, IFN-λ4 may contribute to the development of CTNNB1 mutations and increased risk of HCC in patients without viral clearance.
2021-09-15 | GSE145038 | GEO
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2017-09-14 | GSE84402 | GEO
Project description:Objective: To evaluate gene expression profiles in patients with advanced cirrhosis compared with healthy controls (HC). Results: Patients with advanced cirrhosis exhibit an unbalanced systemic response involving pro-fibrotic / protective signatures that could be contributing to the pathogenesis of cirrhosis and also to that of the extra-hepatic complications of this disease.
2016-02-14 | E-MTAB-3338 | biostudies-arrayexpress
Project description:Metformin is a hypoglycaemic agent used to treat type 2 diabetes mellitus (DM2) patients, with a broad safety profile. Since previous epidemiological studies had shown that incidence of hepatocellular carcinoma (HCC) decreased significantly in metformin treated DM2 patients, we hypothesized that intervention with metformin could reduce the risk of neoplastic transformation of hepatocytes. HCC is the most common primary liver malignancy and it generally originates in a background of liver fibrosis and cirrhosis. In the present study, we took advantage of a transgenic mouse (TG221) characterized by microRNA-221 overexpression, with cirrhotic liver background induced by chronic administration of carbon tetrachloride (CCl4). This mouse model develops fibrosis, cirrhosis and liver tumors that become visible in 100% of mice at 5-6 months of age.
2019-06-03 | GSE131175 | GEO
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
2013-08-30 | E-GEOD-49542 | 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. 156 primary tissues and 25 cultured normal and HCC cell lines
2014-09-16 | E-GEOD-60753 | biostudies-arrayexpress
Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens
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