Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Characterization of gene expression profile in HBV-related liver fibrosis patients

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Mingjie Wang

PROVIDER: E-GEOD-84044 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis.

Wang Mingjie M Gong Qiming Q Zhang Jiming J Chen Liang L Zhang Zhanqing Z Lu Lungen L Yu Demin D Han Yue Y Zhang Donghua D Chen Peizhan P Zhang Xiaonan X Yuan Zhenghong Z Huang Jinyan J Zhang Xinxin X

Scientific reports 20170306

Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV infected patients. Through integrative data analysis, we identified several pathways and key genes involved in the initiation and exacerbation of liver ...[more]

PMID: 28262670

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Project description:Hepatitis B virus (HBV) causes both acute and chronic liver inflammation. Approximately 600,000 CHB patients each year die of HBV-related diseases such as cirrhosis and liver cancer. Therefore, CHB remains a global health concern. Although there have been anti-HBV agents for treating CHB, they have some limitations including viral-drug resistance and adverse effects. Type III IFN or IFN-λ is promising to use as anti-HBV agents because of its anti-viral activities like type I IFNs. In addition, the expression of its receptor, IFNLR1, is limited only in epithelial cells including hepatocytes. Thus, treatment with IFN-lambda results in less side effects compared to IFN-alpha treatment. IFN-lambdas have been shown to inhibit the replication of several viruses including IAV, DENV, EMCV, HIV, HCV, and HBV; however, there have been no studies on the effects of IFN-λ3, the highest activity among other subtypes, on HBV replication. Therefore, this study aims to determine antiviral activities of IFN-λ3 against HBV replication and to investigate its molecular mechanism responsible for suppressing HBV propagation. The results showed that HBV transcripts and amount of intracellular HBV DNA were decreased in HepG2.2.15 cells, stable HBV-transfected hepatoblastoma cell line, treated with IFN-λ3 in a dose-dependent manner. This indicated that IFN-λ3 could inhibit HBV replication. Next, we performed quantitative proteomics to investigate the proteome changes in HepG2.2.15 treated with IFN-λ3. The proteins that changed their expressions were involved in several biological processes such as defense to viral infection, immune responses, cell-cell adhesion, transcription, translation, and metabolism. We further confirmed the proteomics results by immunoblotting assay. Consistent with MS data, it found that the expression of OAS3, SAMHD1 and STAT1 were increased as a result of IFN-λ3 stimulation. These results indicated that proteomics results were reproducible and reliable. Finally, we proposed 3 possible mechanisms involved in suppressing HBV replication including i.) IFN-λ3 induced anti-viral proteins affecting many steps in HBV life cycle ii.) IFN-λ3 promoted antigen processing and antigen presentation and iii.) IFN-λ3 rescued RIG-I signaling to promote both type I and type III IFN production.

Dataset Information

Characterization of gene expression profile in HBV-related liver fibrosis patients

Publications

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis.

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