河北医科大学学报 ›› 2024, Vol. 44 ›› Issue (5): 501-507.doi: 10.3969/j.issn.1007-3205.2024.05.002

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基于基因表达谱探讨儿童肺炎关键基因及通路

  

  1. 郑州大学附属儿童医院检验科,郑州市儿童感染与免疫重点实验室,河南 郑州 450000

  • 出版日期:2024-05-25 发布日期:2024-05-22
  • 作者简介:弓伟华(1995-),女,河南郑州人,郑州大学附属儿童医院,郑州市儿童感染与免疫重点实验室临床医学检验技师,医学硕士,从事免疫学检验和肿瘤免疫研究。

Investigation intokey genes and pathways of pneumonia in children based on gene expression profile

  1. Department of Clinical Laboratory and Immunity, Children′s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children′s Infection  Henan Province, Zhengzhou 450000, China

  • Online:2024-05-25 Published:2024-05-22

摘要: 目的 儿童肺炎是呼吸道常见炎症性疾病,是全球5岁以下儿童常见死因。探索儿童肺炎早期诊断关键基因及通路对研究肺炎发病机制具有重要意义。
方法 从基因表达谱(gene wxpression omnibus,GEO)数据库筛选儿童肺炎数据集,通过GEO2R筛选差异基因(differentially expressed genes,DEGs),对DEGs进行分析筛选关键基因和核心基因。最后,通过GSE42834验证集进行受试者工作特征(receiver operating characteristic, ROC)曲线分析。
结果 共获得375个DEGs,其中96个上调,279个下调。基因本体(geneontology, GO)分析揭示差异基因主要在免疫效应过程、细胞活化、细胞分泌、免疫分子结合、补体受体活性等富集;京都基因与基因组百科全书(kyotoencyclopedia of genes and genomes, KEGG)分析提示差异基因主要在免疫和感染性疾病通路富集。通过蛋白互作分析获得前5位关键基因,分别是HLA-A、MAPK14、CD8A、HIST2H2AC、IL2RB,ROC曲线分析揭示MAPK14、CD8A、HIST2H2AC和IL2RB基因的AUC均>0.7;进一步分析提示IL2RB可能是通过调控JAK-STAT信号通路参与肺炎发病机制的核心基因。
结论 HLA-A、MAPK14、CD8A、HIST2H2AC、IL2RB是儿童肺炎早期诊断关键基因,核心基因IL2RB通过调控JAK-STAT信号通路参与儿童肺炎发病机制。


关键词: 肺炎, 基因表达, 儿童

Abstract: Objective Pneumonia in children is a common inflammatory disease of the respiratory system and the most common cause of death in children under 5 years worldwide. Exploring the key genes and pathways of early diagnosis of pneumonia in children is of great significance for studying the pathogenesis of pneumonia. 
Methods The dataset was screened from Gene Expression Omnibus (GEO) database, and differentially expressed genes were screened by GEO2R. Key genes and core genes of DEGs were analyzed and screened. Finally, the receiver operating characteristic (ROC) curve analysis was conducted using GSE42834 dataset. 
Results A total of 375 DEGs were obtained, of which 96 were up-regulated and 279 were down-regulated. Geneontology (GO) analysis revealed that DEGs were mainly enriched in immune effector process, cell activation, cell secretion, immune molecule binding, and complement receptor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that DEGs were mainly enriched in immune and infectious disease pathways. The top 5 key genes were identified through Protein Protein Interaction (PPI) analysis, namely HLA-A, MAPK14, CD8A, HIST2H2AC, and IL2RB. The areas under ROC curve of MAPK14, CD8A, HIST2H2AC and IL2RB were all greater than 0.7, which showed good diagnostic value. Further analysis suggested that IL2RB might be the core gene involved in the pathogenesis of pneumonia by regulating the JAK-STAT signaling pathway. 
Conclusion HLA-A, MAPK14, CD8A, HIST2H2AC and IL2RB are key genes for early diagnosis of pneumonia in children. IL2RB, the core gene, participates in the pathogenesis of pneumonia in children by regulating the JAK-STAT signaling pathway.


Key words: pneumonia, gene expression; child