Molecular characterization of chronic liver disease dynamics: from liver fibrosis to acute-on-chronic liver failure
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PROVIDER: PRJNA580468 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND: The molecular mechanisms driving the progression from early chronic liver disease (eCLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Thus, the aim of this work is to develop a network-based approach to investigate molecular pathways driving progression from eCLD to ACLF. We created 9 liver-specific biological networks capturing key pathophysiological processes potentially related to CLD. We used these networks as framework to perform gene set enrichment analyses(GSEA) and create dynamic profiles of disease progression. RESULTS: Principal component analyses revealed that samples clustered according to the disease stage. GSEA analyses of the defined processes showed an up-regulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between CC and DC, while ACLF showed acute expression changes in all the defined liver-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated to ACLF onset. Functional analyses showed that ascending profiles were associated to inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the up-regulation of 4 genes of the ascending profile CXCL-6, KRT-18, SPINK-1, and ITGA2, and validated our findings on an independent patient’s cohort. CONCLUSION: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis processes. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting thus the hypothesis that ACLF should be considered a distinct entity.
2021-09-11 | GSE139602 | GEO
Project description:Serum EV proteome target analysis of liver fibrosis in chronic hepatitis C patients was performed.
2023-01-27 | PXD031289 | JPOST Repository
Project description:Serum EV proteome non-target analysis of liver fibrosis in chronic hepatitis C patients was performed using TMT-tag quantitation.
2023-01-26 | PXD031283 | JPOST Repository
Project description:Background & aimsThe molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progression from early-CLD to ACLF.MethodsTranscriptome analysis was performed on liver biopsies from patients at different liver disease stages, including fibrosis, compensated cirrhosis, decompensated cirrhosis and ACLF, and control healthy livers. We created 9 liver-specific disease-related protein-protein interaction networks capturing key pathophysiological processes potentially related to CLD. We used these networks as a framework and performed gene set-enrichment analysis (GSEA) to identify dynamic gene profiles of disease progression.ResultsPrincipal component analyses revealed that samples clustered according to the disease stage. GSEA of the defined processes showed an upregulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between compensated and decompensated cirrhosis, while ACLF showed acute expression changes in all the defined liver disease-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated with ACLF onset. Functional analyses showed that ascending profiles were associated with inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the upregulation of genes of the ascending profile and validated our findings in an independent patient cohort.ConclusionACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting the hypothesis that ACLF should be considered a distinct entity.Lay summaryBy using transjugular biopsies obtained from patients at different stages of chronic liver disease, we unveil the molecular pathogenic mechanisms implicated in the progression of chronic liver disease to cirrhosis and acute-on-chronic liver failure. The most relevant finding in this study is that patients with acute-on-chronic liver failure present a specific hepatic gene expression pattern distinct from that of patients at earlier disease stages. This gene expression pattern is mostly related to inflammation, fibrosis, angiogenesis, and senescence and apoptosis pathways in the liver.
| S-EPMC9079303 | biostudies-literature
Project description:development of prognostic biomarkers for HBV-related acute-on-chronic liver failure
2020-03-07 | PXD017928 |
Project description:Neutrophil Gene expression in Acute-on-chronic liver failure (ACLF), Chronic liver disease (CLD) and Healthy Controls_AIIMSND_Aug2020
| PRJNA657743 | ENA
Project description:Hepatitis B virus (HBV) infection is a leading risk factor for liver fibrosis (LF) and hepatocellular carcinoma. Emerging evidence indicates that host genetic, virological and immunological factors will influence the fibrotic progress. Many previous studies have focused on specific pathways or genes included in LF mechanism, however global view of the whole genome expresion profile in HBV related LF patients never been studied, and the mechanisms underlying the promotion of liver fibrosis progression remain obscure. Here we collected liver biopsy samples from 124 chronic hepatitis B (CHB) patients and used Affymetrix HG U133 Plus 2.0 microarray to quantify the transcriptome of these patients. Through integrated data analysis, including geneset enrichment analysis (GSEA), weighted gene co-expression analysis (WGCNA), differential expressed gene (DEG) screening, trend test, principle component analysis (PCA) etc., we identified several key pathways and hub genes participated in the initiation and exacerbation of liver fibrotic progress. The function of these hub genes were also validated by in vitro and in vivo experiments using HepG2, Huh7 and LX-2 cell lines and transgenic mice. This is the first large-scale study investigating the gene expression profile in HBV-related LF patients which will be crucial for unlocking the gene functions and gene-gene correlations in fibrosis progress. Liver biopsy samples from 124 CHB patients were collected. The pathological Scheuer Score of each sample were evaluated base on the inflamation and fibrosis severity. Gene expresson of samples in different stage were compared and analyzed. This dataset is part of the TransQST collection.
2016-08-21 | E-GEOD-84044 | biostudies-arrayexpress
Project description:Liver fibrosis was found to be existed in all kinds of chronic liver diseases. Many studies suggested that DNA methylation was related with the pathogenesis of liver fibrosis. The aim of this study was to quantitatively detect DNA methylation changes in the whole genome in fibrotic liver tissues. Carbon tetrachloride (CCl4) was used to induce male mice liver fibrosis by intraperitoneal injection for 4 weeks. A genome-wide methylome analysis was performed using 850K BeadChips assays. The methylation status of 27 CpG dinucleotides located in 3 genes was detected by pyrosequencing to confirm chips data accuracy, and their mRNA expressions were examined by RT-qPCR methods. A total of 130,068 differentially methylated sites (DMS, 58,474 hypermethylated and 71,594 hypomethylated) between fibrotic liver tissues and control mice liver tissues were identified by the 850k BeadChips array. They distribute in each chromosome. Recognition of apoptotic cell, Notch and p38MAPK et al activities were significantly enriched in the Gene Ontology (GO) analyses. Cholesterol metabolism, bile secretion and more biosynthesis and metabolism pathway were enriched in KEGG pathway analyses. Many classical pathways of fibrogenesis and liver activity, as well as more biosynthetic and metabolic pathways, were found to be related to methylation changes. Our result facilitates future research for clinical application.
2023-01-11 | GSE193182 | GEO
Project description:Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients
| PRJNA674765 | ENA