Digital Gene Expression profiles analysis of patients with HCV-related hepatic fibrosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE154055 | GEO | 2020/09/10
REPOSITORIES: GEO
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Project description:Introduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression, using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChip™ System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis. Keywords: HCV-advance disease state
2007-11-01 | GSE7741 | GEO
Project description:Introduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression, using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChip⢠System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis. Experiment Overall Design: Liver biopsy samples were collected from patients of (a) HCV-infected early disease stage (HCV-E, control 1) (b) non-HCV advance disease stage (control 2) and (c) HCV-infected advance disease stage (HCV-A) for RNA extraction. Equal amount of RNA was pooled from samples (n=4)within each group and hybridized to HG-U133 Plus 2.0 array.
2008-06-15 | E-GEOD-7741 | biostudies-arrayexpress
Project description:Although treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in high rates of cure, liver fibrosis does not resolve immediately after HCV eradication. Resolution of fibrosis occurs in some, but not all patients, after HCV cure, and hepatic decompensation and hepatocellular carcinoma can still occur in patients with pre-existing cirrhosis. We hypothesized that evaluation of the host liver proteome in the context of HCV treatment would provide insight into how inflammatory and fibrinogenic pathways change upon HCV eradication. We evaluated the whole liver proteome and phosphoproteome using paired liver biopsies from 8 HCV-infected patients collected before or immediately after treatment with DAAs in clinical trials. We identify interferon stimulated proteins as the predominant pathways that decrease with HCV treatment, which is consistent with previous analyses of the liver transcriptome during DAA therapy. While there was no change in the proteome of pathways associated with liver fibrosis, we identified a decrease in the phosphoproteome signature for ERK1/ERK2 as a result of HCV treatment. Conclusion: There is a reduction in the endogenous interferon-mediated antiviral response and alterations in the phosphoproteome that may precede resolution of fibrosis in the liver immediately after treatment of HCV with DAAs.
2023-03-11 | PXD024846 | Pride
Project description:Hepatic complications of HCV infection, including fibrosis and cirrhosis are accelerated in HIV-infected individuals. Although liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling error. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using SELDI-TOF MS.
2018-04-09 | PXD009007 | Pride
Project description:<p>Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects.</p> <p>Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (<i>ENG</i>) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific <i>ENG</i> variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39-6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.</p>
| phs001902 | dbGaP
Project description:A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS.
2017-06-21 | PXD005777 | Pride
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection. We aimed to identify differential gene expression associated with GBV-C in HCV/HIV co-infection by comparing RNA expression from liver biopsies of HCV/HIV co-infected patients with and without GBV-C infection. Liver biopsies were obtained from 10 Patients with HCV/HIV co-infection; 4 of these patients were positive for GBV-C infection and 6 were negative for GBV-C infection. The tissue was stored in RNAlater and RNA was extracted for hybridisation to Affymetrix Human Genome U133 plus 2.0 microarrays at the University of Texas Medical Branch Molecular Genomics Core Laboratory. The data was analysed for genes differentially expressed between GBV-C positive and negative patients using Partek Genomics suite and applying a custom CDF file (Hs133P_Hs_UG_8), available from Molecular and Behavioural Neuroscience Institute, University of Michigan.
2011-05-10 | E-GEOD-16593 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) chronically infects 170 million people worldwide and is a leading cause of liver-related mortality due to hepatocellular carcinoma and cirrhosis1. Standard-of-care treatment is shifting from interferon-alpha (IFNM-NM-1)-based to IFNM-NM-1-free directly acting antiviral (DAA) regimens, which demonstrate improved efficacy and tolerability in clinical trials2,3. Virologic relapse after completion of DAA therapy is a common cause of treatment failure, although mechanisms are unclear2,3. We conducted a clinical trial using the DAA sofosbuvir with ribavirin (SOF/RBV)4, and report here detailed mRNA expression analysis of pre- and end-of-treatment (EOT) liver biopsies and blood samples. On-treatment viral clearance was accompanied by rapid down-regulation of interferon-stimulated genes (ISGs) in liver and blood. Analysis of paired liver biopsies from patients who achieved a sustained virologic response (SVR) revealed that viral clearance was accompanied by decreased expression of ISGs, IFNG, and IFNLs, but increased expression of IFNA2. Patients who achieved SVR had higher expression of a hepatic type-I interferon gene signature in unpaired EOT liver biopsies than patients who later relapsed. Together, these results support a model whereby restoration of type-I intrahepatic interferon signaling at the EOT is associated with sustained hepatic HCV suppression and prevention of relapse upon withdrawal of SOF/RBV. Sustained Virologic Response for Chronic Hepatitis C Patients Treated with Sofosbuvir and Ribavirin
2014-08-15 | E-GEOD-51699 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) remains a significant public health threat as new 1.75 million HCV infections emerged worldwide. The majority of these infections become persistently infected, while around 30 % spontaneously eliminate the virus. Clinical factors for viral clarification are related to HCV interaction with host immune system, but little is known about the consequences after HCV spontaneous resolution. These individuals are difficult to recruit and study as acute infection is usually asymptomatic, and they will not be identified unless it progress to chronic infection. The study of peripheral blood mononuclear cells (PBMCs) of these patients is crucial, as PBMCs are one of the main HCV extrahepatic reservoirs, and its transcriptional profile provide us information of innate and adaptive immune response against HCV infection. Our research shows novel insight on molecular consequences of spontaneous resolution after an acute HCV infection. 96 Individuals with different HCV exposure status were recruited: spontaneous resolved, chronic infected and healthy controls; and the microRNA profile of their PBMCs were analyzed. Our results indicate similar disruption of miRNA expression on HCV chronic patients and those who spontaneously clarified the infection, compared to control patients. The disrupted miRNAs formed a signature of 21 miRNAs that mainly regulate lipid metabolism. This is the first report showing miRNA profile similarities between chronic HCV patients and spontaneous resolved individuals. Thus, our results suggest that HCV infection promotes molecular alterations in PBMCs that will last longer after HCV spontaneous eradication. This evidences open up new prospects in the management of individuals who spontaneously clarified infection, as they should be monitored and followed to dismiss future HCV-related complications, such us liver diseases complications. The identified miRNA signature could be used as biomarker to monitor HCV fingerprint on HCV-exposed patients.
2019-06-21 | E-MTAB-8023 | biostudies-arrayexpress
Project description:A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS.
2020-03-12 | MSV000085094 | MassIVE