对多个基因表达综合数据集的系统分析揭示了乙型肝炎病毒

StephenW

Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus-related acute liver failure
Huadi Chen  1   2   3 , Wenting Zhao  4 , Yixi Zhang  5 , Yiwen Guo  1   2   3 , Weixin Luo  1   2   3 , Xiaobo Wang  1   2   3 , Yu Nie  1   2   3 , Maodong Ye  1   2   3 , Changjun Huang  1   2   3 , Dongping Wang  1   2   3 , Maogen Chen  1   2   3 , Xiaoshun He  1   2   3 , Qiang Zhao  1   2   3
Affiliations
Affiliations

    1
    Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
    2
    Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.
    3
    Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
    4
    School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
    5
    Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

    PMID: 32686296 DOI: 10.1111/jcmm.15561

Abstract

Acute liver failure (ALF) caused by hepatitis B virus (HBV) is common type of liver failure in the world, with high morbidity and mortality rates. However, the prevalence, genetic background and factors determining the development of HBV-related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV-related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV-ALF. We found 1277 genes were co-up-regulated and that 1082 genes were co-down-regulated in the 3 data sets. Inflammation-related pathways were enriched in the co-up-regulated genes and synthetic metabolic pathways were enriched in the co-down-regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune-driven mechanism of HBV-ALF and 10 hub genes based on gene expression profiles.

Keywords: HBV-ALF; WGCNA; bioinformatics analysis; immune; inflammation.

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

StephenW

对多个基因表达综合数据集的系统分析揭示了乙型肝炎病毒相关的急性肝衰竭的剧烈免疫反应
陈华迪1 2 3，赵文婷4，张一喜5，郭一文1 2 3，罗维新1 2 3，王晓波1 2 3，聂妮1 2 3，茂东野1 2 3，黄昌俊1 2 3，王东平1 2 3陈茂根1 2 3何小顺1 2 3赵强1 2 3
隶属关系
隶属关系

    1个
    中山大学附属第一医院器官移植中心，中国广州
    2
    广东省器官捐赠与移植免疫学广东省重点实验室
    3
    中国广东省国际科学技术合作基地（器官移植），广州。
    4
    南方医科大学中医药学院，广州
    5
    首都医科大学附属北京友谊医院肝移植中心，北京

    PMID：32686296 DOI：10.1111 / jcmm.15561

抽象

由乙型肝炎病毒（HBV）引起的急性肝衰竭（ALF）是世界上常见的肝衰竭类型，其发病率和死亡率很高。然而，很少研究HBV相关ALF的发生率，遗传背景和决定其发展的因素。在这项研究中，我们通过生物信息学分析检查了三个基因表达综合（GEO）数据集，以确定差异表达的基因（DEG），关键的生物学过程和途径。免疫浸润分析显示在HBV相关的ALF组织中有较高的免疫细胞浸润。然后，我们通过免疫组织化学测定法确认了临床样品中的自然杀伤细胞和巨噬细胞浸润，这暗示这些细胞在HBV-ALF中起重要作用。我们发现在3个数据集中共有1277个基因被共同上调，而共有1082个基因被共同下调。炎症相关途径丰富了共同上调的基因，而合成代谢途径丰富了共同下调的基因。 WGCNA还揭示了丰富的免疫炎症反应关键模块，并鉴定了10个中枢基因，它们在独立的数据集中差异表达。总之，我们基于基因表达谱鉴定了激烈的免疫炎症反应，以阐明HBV-ALF和10个中枢基因的免疫驱动机制。

关键字：HBV-ALF； WGCNA；生物信息学分析；免疫炎。

©2020作者。细胞与分子医学基金会和约翰·威利父子有限公司出版的《细胞与分子医学杂志》。

StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.15561