酒精性肝炎自噬关键基因的筛选及生物信息学分析

Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis

    摘要
  • 摘要:
      目的   筛选酒精性肝炎（AH）的自噬关键基因，探讨AH潜在的生物标志物和治疗靶点。
      方法  采用基因表达综合数据库（GEO）中的2个AH基因芯片和从MSigDB、GeneCards数据库中获得的自噬相关数据集，通过加权基因共表达网络分析（WGCNA）获取关键基因。对筛选的关键基因进行基因本体（GO）、京都基因和基因组百科全书（KEGG）功能富集分析，蛋白质相互作用（PPI）分析，免疫浸润分析，构建信使RNA（mRNA）-微小RNA（miRNA）网络，进行酒精性肝病不同分期的自噬相关关键基因的表达差异分析，并进一步通过实时荧光定量逆转录聚合酶链反应（RT-qPCR）在AH患者和小鼠肝脏组织中验证。
      结果  本研究筛选得到了11个与AH自噬相关的基因（EEF1A2、CFTR、SOX4、TREM2、CTHRC1、HSPB8、TUBB3、PRKAA2、RNASE1、MTCL1、HGF），均为上调基因。在AH患者和小鼠肝脏组织中，SOX4、TREM2、HSPB8、PRKAA2在AH组中的相对表达量均高于对照组。
      结论  SOX4、TREM2、HSPB8、PRKAA2可能是AH潜在的生物标志物和治疗靶点。

     

    Abstract:
      Objective  To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH.
      Methods  Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice.
      Results  Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group.
      Conclusions  SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

     

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