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Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus-related acute liver failure.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-07-19 , DOI: 10.1111/jcmm.15561
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
Affiliation  

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.

中文翻译:

对多个 Gene Expression Omnibus 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强烈免疫反应。

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,发病率和死亡率都很高。然而,很少研究 HBV 相关 ALF 的患病率、遗传背景和决定因素。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,以识别差异表达基因 (DEG)、关键生物过程和途径。免疫浸润分析显示 HBV 相关的 ALF 组织中存在高免疫细胞浸润。然后,我们通过免疫组织化学分析证实了临床样本中的自然杀伤细胞和巨噬细胞浸润,表明这些细胞在 HBV-ALF 中发挥重要作用。我们发现在 3 个数据集中有 1277 个基因共同上调,1082 个基因共同下调。炎症相关通路富含共调基因,合成代谢途径富含共下调基因。WGCNA 还揭示了一个富含免疫炎症反应的关键模块,并确定了 10 个中枢基因,在独立数据集中差异表达。总之,我们根据基因表达谱确定了强烈的免疫炎症反应,以阐明 HBV-ALF 和 10 个枢纽基因的免疫驱动机制。
更新日期:2020-07-19
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