基于生物信息学分析鉴定哮喘潜在的关键自噬和铁死亡相关基因

doi:10.6040/j.issn.1671-7554.0.2024.1056

摘要/Abstract

摘要： 目的利用生物信息学分析方法,鉴定自噬和铁死亡过程的共同哮喘基因。方法从基因表达综合(Gene Expression Omnibus, GEO)数据库中获取哮喘相关的GSE74986数据集,利用GEO2R在线工具进行分析,通过设定|log₂ FC|≥1和P_校正< 0.05的标准,筛选出差异表达基因(differential expression genes, DEGs)。使用韦恩图获得重叠的铁死亡和自噬相关DEGs。进行功能和通路富集分析、蛋白质-蛋白质相互作用网络分析和Cytoscape软件算法鉴定枢纽基因。构建转录因子(transcription factor, TF)、miRNA与枢纽基因之间的相互作用网络。分析枢纽基因在哮喘组织中免疫细胞浸润情况。通过受试者工作特征(receiver operating characteristic, ROC)曲线分析来验证枢纽基因的诊断价值。动物实验验证枢纽基因。结果共鉴定出105个自噬相关的DEGs 和 37个铁死亡相关的DEGs。这些 DEGs 分别参与自噬、PI3K-Akt、铁死亡、PPAR等信号通路。筛选出10个枢纽基因(HSPA8、NPM1、HNRNPA2B1、HNRNPA1、HSPA5、EEF1A1、G3BP1、TFRC、GABARAPL1和XBP1),其可靶向61种miRNAs和17种TFs。免疫浸润分析表明,枢纽基因与M0型巨噬细胞、活化的NK细胞及 M1型巨噬细胞之间存在相关性。ROC曲线分析结果表明,枢纽基因在哮喘诊断中具有较高价值。动物实验证实,模型组肺组织中HSPA8、NPM1、HNRNPA2B1、HNRNPA1、HSPA5的蛋白表达水平低于正常组。结论筛选的枢纽基因HSPA8、NPM1、HNRNPA2B1、HNRNPA1、HSPA5、EEF1A1、G3BP1、TFRC、GABARAPL1和XBP1可能是哮喘患者的潜在治疗靶点。

关键词: 哮喘, 基因表达综合数据库, 铁死亡, 自噬, 生物信息学

Abstract: Objective To identify the common asthma genes involved in autophagy and ferroptosis processes using bioinformatics analysis methods. Methods The asthma-related GSE74986 dataset were obtained from the Gene Expre-ssion Omnibus(GEO)database and analyzed using the GEO2R web tool. The differentially expressed genes(DEGs)were screened by setting the criteria of |log₂ FC| ≥ 1 and a corrected P-value <0.05. Ferroptosis- and autophagy-related DEGs were intersected with Venn diagrams. Hub genes were further identified with functional and pathway enrichment analysis, protein-protein interaction network analysis, and algorithms in Cytoscape software, followed by the construction of a transcription factor-miRNA-hub gene interaction network. Hub genes were subjected to immune cell infiltration analysis in asthmatic patients. In addition, the diagnostic value of hub genes was assessed with receiver opera-ting characteristic(ROC)curves analyses. Animal experiments were conducted to validate hub genes. Results A total of 105 autophagy-related DEGs and 37 ferroptosis-related DEGs were identified, which were involved in autophagy-animal, PI3K-Akt pathway, ferroptosis, and PPAR pathway. Ten hub genes were yielded, including HSPA8, NPM1, HNRNPA2B1, HNRNPA1, HSPA5, EEF1A1, G3BP1, TFRC, GABARAPL1, and XBP1 targeting a total of 61 miRNAs and 17 TFs. Immune cell infiltration analysis showed that these hub genes were closely related to macrophages M0, activated NK cells, and macrophages M1. ROC curve analyses indicated the high diagnostic value of the hub genes for asthma. Animal experiments confirmed that the protein expression levels of HSPA8, NPM1, HNRNPA2B1, HNRNPA1, and HSPA5 in the lung tissue of the model group were significantly lower than those in the normal group. Conclusion The screened hub genes,including HSPA8, NPM1, HNRNPA2B1, HNRNPA1, HSPA5, EEF1A1, G3BP1, TFRC, GABARAPL1, and XBP1, may be potential therapeutic targets for asthma.

Key words: Asthma, Gene Expression Omnibus database, Ferroptosis, Autophagy, Bioinformatics

中图分类号:

R574

张秋萍,朱慧志,吕川,夏咏琪,张秀. 基于生物信息学分析鉴定哮喘潜在的关键自噬和铁死亡相关基因[J]. 山东大学学报 (医学版), 2026, 64(1): 74-87.

ZHANG Qiuping, ZHU Huizhi, LYU Chuan, XIA Yongqi, ZHANG Xiu. Identification of potential key autophagy- and ferroptosis-related genes in asthma based on bioinformatics analysis[J]. Journal of Shandong University (Health Sciences), 2026, 64(1): 74-87.

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