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Identifying potential biomarkers in hepatitis B virus infection and its response to the antiviral therapy by integrated bioinformatic analysis |
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| Authors: | Yi He Yingzhi Zhou Huimin Wang Jingyang Yin Yunan Chang Peng Hu Hong Ren Hongmei Xu |
| Institution: | 1. Department of infection, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
Chongqing Key Laboratory of Child Infection and Immunity, Chongqing Medical University, Chongqing, China Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Resources (equal), Software (equal), Validation (equal), Visualization (equal), Writing - original draft (lead);2. Department of infection, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Child Infection and Immunity, Chongqing Medical University, Chongqing, China Contribution: Funding acquisition (equal);3. Chongqing People’s Hospital, Chongqing Medical University, Chongqing, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal), Validation (equal), Writing - original draft (supporting);4. Department of infection, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Child Infection and Immunity, Chongqing Medical University, Chongqing, China Contribution: Data curation (equal), ?Investigation (equal), Resources (equal), Software (equal), Validation (equal), Visualization (equal), Writing - review & editing (equal);5. Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China Contribution: Conceptualization (equal), Writing - original draft (equal);6. Department of infection, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China |
| Abstract: | The antiviral treatment efficacy varies among chronic hepatitis B (CHB) patients and the underlying mechanism is unclear. An integrated bioinformatics analysis was performed to investigate the host factors that affect the therapeutic responsiveness in CHB patients. Four GEO data sets (GSE54747, GSE27555, GSE66698 and GSE66699) were downloaded from the Gene Expression Omnibus (GEO) database and analysed to identify differentially expressed genes(DEGs). Enrichment analyses of the DEGs were conducted using the DAVID database. Immune cell infiltration characteristics were analysed by CIBERSORT. Upstream miRNAs and lncRNAs of hub DEGs were identified by miRWalk 3.0 and miRNet in combination with the MNDR platform. As a result, seventy-seven overlapping DEGs and 15 hub genes were identified including CCL5, CXCL9, MYH2, CXCR4, CD74, CCL4, HLA-DRB1, ACTA1, CD69, CXCL10, HLA-DRB5, HLA-DQB1, CXCL13, STAT1 and CKM. The enrichment analyses revealed that the DEGs were mainly enriched in immune response and chemokine signalling pathways. Investigation of immune cell infiltration in liver samples suggested significantly different infiltration between responders and non-responders, mainly characterized by higher proportions of CD8+ T cells and activated NK cells in non-responders. The prediction of upstream miRNAs and lncRNAs led to the identification of a potential mRNA-miRNA-lncRNA regulatory network composed of 2 lncRNAs (H19 and GAS5) and 5 miRNAs (hsa-mir-106b-5p, hsa-mir-17-5p, hsa-mir-20a-5p, hsa-mir-6720-5p and hsa-mir-93-5p) targeting CCL5 mRNA. In conclusion, our study suggested that host genetic factors could affect therapeutic responsiveness in CHB patients. The antiviral process might be associated with the chemokine-mediated immune response and immune cell infiltration in the liver microenvironment. |
| Keywords: | bioinformatic analysis chronic hepatitis B immune cell infiltration lncRNA miRNA therapeutics |