Identifying potential biomarkers in hepatitis B virus infection and its response to the antiviral therapy by integrated bioinformatic analysis

作者全名："He, Yi; Zhou, Yingzhi; Wang, Huimin; Yin, Jingyang; Chang, Yunan; Hu, Peng; Ren, Hong; Xu, Hongmei"

作者地址："[He, Yi; Zhou, Yingzhi; Wang, Huimin; Chang, Yunan; Xu, Hongmei] Chongqing Med Univ, Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Dept Infect,Childrens Hosp, Chongqing, Peoples R China; [He, Yi; Zhou, Yingzhi; Wang, Huimin; Chang, Yunan; Xu, Hongmei] Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China; [Yin, Jingyang] Chongqing Med Univ, Chongqing Peoples Hosp, Chongqing, Peoples R China; [Hu, Peng; Ren, Hong] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Dept Infect Dis, Affiliated Hosp 2,Minist Educ,Inst Viral Hepatiti, Chongqing, Peoples R China"

通信作者："Xu, HM (corresponding author), Chongqing Med Univ, Childrens Hosp, 136 Zhongshan Rd, Chongqing 400014, Peoples R China."

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000654629800001

JCR分区：Q2

影响因子：5.3

年份：2021

卷号：25

期号：14

开始页：6558

结束页：6572

文献类型：Article

关键词：bioinformatic analysis; chronic hepatitis B; immune cell infiltration; lncRNA; miRNA; therapeutics

摘要："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."

基金机构：National Science and Technology Major Project of China [2017ZX10202203007008]

基金资助正文：This study was funded by the National Science and Technology Major Project of China [2017ZX10202203007008]