Transcriptome analysis of liver cirrhosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210545 | GEO | 2025/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:Background & aims: The role of microRNAs (miRNAs) in Alcoholic Hepatitis (AH) and their potential as therapeutic targets in liver disease has not been explored yet. This study aims at profiling miRNA in AH and identifying dysregulated miRNAs involved in AH pathophysiology. Methods: miRNA expression arrays were performed in 13 AH, 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples. Genome wide expression profile was retrieved for 12 paired AH and control samples. MiRNA and mRNA expression data was integrated and identified miRNAs were validated in AH samples and in animal models of liver injury. Results: The miRNA array showed 111 upregulated and 66 downregulated miRNAs in AH versus healthy subjects. The comparison of miRNA profile in liver samples from AH among ALD-CH, HCV-CH and NASH-CH identified 18 miRNAs specifically dysregulated in AH. Integrative miRNA and mRNA analysis in AH identified dysregulated miRNAs for which their target genes were also dysregulated. A functional analysis of identified miRNAs and their targets revealed their involvement in the regulation of canonical pathways related to apoptosis, fatty acid metabolism and cell cycle among others. miRNAs expression (miR-182, miR-21, miR-155, miR-214, miR-432, miR-422a) was validated in an independent cohort of AH. MiR-182 expression correlated with cholestasis, disease severity and short-term mortality. Moreover, miR-182 expression is associated to cholestasis with ductular reaction but not to fibrosis and inflammation in animal models of liver injury. Conclusions: AH is characterized by an important dysregulation of miRNA expression with a unique miRNA profile. MiRNAs specifically expressed in AH are associated to cholestasis⦠Uncovered miRNAs are involved in important pathophysiological features in AH suggesting ta regulation of he role of miRNAs in the regulation of AH, and highlight miR-182 as a potential regulator of its pathophysiology. miRNA expression arrays were performed in 13 AH(Alcoholic hepatitis), 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples(CTRL).
2016-08-02 | E-GEOD-59492 | biostudies-arrayexpress
Project description:<p>There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis and monitoring disease progression. In this study we evaluated cerebrospinal fluid (CSF) proteins, which are known to be critically involved in PD or identified in our preliminary profiling studies, aptamers, and RNAs as potential PD biomarkers. Access to subjects for this study was via the Pacific Northwest Udall Center (PANUC) and the Alzheimer's Disease Research Center (ADRC) at the University of Washington and Oregon Health and Sciences University (OHSU). Using CSF samples from 30 well-characterized patients with PD and 30 age-, sex-matched healthy controls, we prepared RNA seq libraries and performed deep sequencing of all RNA species, including small and long RNA, mRNAs, noncoding RNAs and differentially spliced transcripts. We then tried several methods for RNAseq data analysis to optimize our analysis pipeline. We identified a total of 3381 transcripts corresponding to 182 long intergenic RNAs (LincRNAs), 11 microRNAs (miRNAs), 2861 protein-coding transcripts, 200 pseudogenes and 127 antisense RNAs; some of them were differentially expressed between PD and control groups. Selected differentially expressed RNAs have been validated in the same set of CSF samples using real-time PCR (RT-PCR). Further validations in independent, larger cohorts of samples are still ongoing. Our results obtained so far suggested that CSF proteins and RNAs could be used as good indexes for PD diagnosis and disease severity/progression. This study is a part of the NIDDS-funded Parkinson's Disease Biomarkers Program (PDBP).</p>
| phs000901 | dbGaP
Project description:Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among the patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care, reduce morbidity and mortality. This is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to detect differentially expressed proteoforms (DEPs) in the plasma of patients with cirrhosis with the goal to identify candidate biomarkers of disease progression. 663 DEPs were identified across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the progressive stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in numerous metabolic, oxidative, immunological, and hematological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
2024-03-13 | MSV000094311 | MassIVE
Project description:Background: Several studies have investigated the association of miRNAs with hepatocellular carcinoma (HCC) but the data are not univocal. Methods: We performed a microarray study of miRNAs in hepatitis C virus (HCV)-associated HCC and other liver diseases and healthy conditions. Results and Conclusions: The simultaneous comparison of different liver diseases and normal livers allowed the identification of 18 miRNAs exclusively expressed in HCV-associated HCC, with sensitivity and specificity values of diagnostic-grade. A total number of 76 liver specimens obtained from 43 patients were analyzed: 26 liver specimens obtained from 10 patients with HCV-associated HCC, including 9 specimens from the tumor area (HCC) and 17 specimens from the surrounding non-tumorous tissue affected by cirrhosis (HCC-CIR); 18 specimens from 10 patients with HCV-associated cirrhosis without HCC (CIR); 13 specimens from 4 patients with HBV-associated acute liver failure (ALF); 12 specimens from 12 liver donors (LD); and 7 from normal liver of 7 subjects who underwent hepatic resection for liver angioma (NL).
2013-02-20 | E-GEOD-40744 | biostudies-arrayexpress
Project description:In this study, we compared circulating miRNAs identified in hepatitis C virus (HCV)-infected patients presenting two extremes of liver disease: mild/moderate fibrosis and cirrhosis. The patients in the cirrhosis group subsequently developed hepatocellular carcinoma (HCC). Methods: Expression profile of miRNA were identify by semiconductor sequencing using Ion Proton High Power Sequencer. The sequences were exported in FASTQ format for further analysis using the CLC Genomics Workbench software version 8.5. The transcripts were trimmed and then annotated by comparing sequence similarity to miRBASE. After identification of mature miRNAs, differential expression analysis of miRNAs between the mild fibrosis and cirrhosis groups was performed using Empirical Analysis of Differential Gene Expression (EDGE). To verify the potential target genes regulated by the differentially expressed miRNAs identified between the two groups studied, the miRnet tool version 2.0 was applied to identify the regulatory networks in which the miRNAs are involved. Results: We identified 163 mature miRNAs in the mild/moderate fibrosis group and 171 in the cirrhosis group, with 144 in common to both groups. Differential expression analysis revealed 5 upregulated miRNAs and 2 downregulated miRNAs in the cirrhosis group relative to the mild/moderate fibrosis group. Functional analyses of regulatory networks (target gene and miRNA) identified gene categories involved in cell cycle biological processes and metabolic pathways related to cell cycle, cancer, and apoptosis. Conclusion:These results suggest that the differentially expressed circulating miRNAs observed in this work (miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p and miR -197-3p) may be candidates for biomarkers in the prognosis of liver disease.
2020-11-06 | GSE160879 | GEO
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269011 | GEO
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269013 | GEO
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269012 | GEO
Project description:Background and Aim: Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis. Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=22) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity. Liver tissue was collected from individuals with established cirrhosis who were awaiting liver transplantation (n=22) at the time of their liver transplantation procedure in the operating room. Normal liver tissue (n=12) was obtained from patients undergoing liver resection for metastatic/benign liver lesions with no underlying chronic liver disease
2013-08-15 | E-GEOD-49012 | biostudies-arrayexpress
Project description:Emerging evidence suggests that microRNAs (miRNAs) are crucially involved in pathogenesis of NAFLD. The integrated analysis of expression profiles of miRNAs and mRNAs can be used to identify functional miRNA-target relationships with high precision. The purpose of this study was to provide insights into the immunopathogenesis of NAFLD using this integrated analysis method.Differentially expressed miRNAs and mRNAs of CD4+ T lymphocytes from liver and mesenteric lymph nodes(MLN) of NAFLD and normal mice were analyzed by microarrays and RNA sequencing respectively. Subsequently, the target genes of the differentially expressed miRNAs were predicted and overlapped with the differentially expressed mRNAs. Then, GO and pathway analyses were performed for the intersecting key genes. The microarray analysis indicated that 170 miRNAs and 2,791 mRNAs were significantly dysregulated in CD4+ T lymphocytes from liver between the two groups. Among the 2,791 mRNAs, 911 overlapped with putative miRNA target genes. A pathway analysis showed that the MAPK pathway was consistently enriched in the liver of NAFLD mice. miR-149-3p, miR-663a, miR-1908, miR-2861 and miR-3185 likely play important roles in the regulation of MAPK pathways. Furthermore, the Notch signaling pathway This study provides an integrated dataset of the miRNA and mRNA profiles in NAFLD, and the results demonstrate that not only the MAPK pathway and its related miRNAs but also the Notch pathway may be involved in NAFLD immunological development.
2014-10-23 | GSE62577 | GEO