目的:探讨免疫球蛋白A肾病(IgAN)铁凋亡的关键基因和潜在分子通路。方法:在基因表达综合(GEO)和FerrDb数据库中获得IgAN数据集和铁凋亡相关基因(FRG)。使用R软件鉴定差异表达的基因(DEGs)并与FRGs相交以获得差异表达的FRGs(DE-FRGs)。之后,在DE-FRGs上进行了京都基因和基因组百科全书(KEGG)途径富集分析(PEA)和基因本体论(GO)功能注释。在检索相互作用基因的搜索工具(STRING)网站中,我们构建了一个蛋白质-蛋白质相互作用(PPI)网络。通过Cytoscape软件筛选hub基因,进一步研究了PPI网络。然后对核心基因进行基因集富集分析(GSEA)。最后,分析样品中的免疫浸润,并分析了hub基因与免疫细胞的相关性。结果:共鉴定出347个DEG。CD44,CDO1,CYBB,IL1B,RRM2,AKR1C1,激活转录因子-3(ATF3),CDKN1A,GDF15,JUN,MGST1,混合,MT1G,NR4A1、PDK4、TNFAIP3和ZFP36被确定为DE-FRG。JUN,IL1B,然后筛选ATF3作为hub基因。GSEA和免疫浸润分析显示hub基因与NOD样受体信号等免疫炎症反应密切相关,IL-17信号,和TNF信号。结论:我们的结果表明,JUN和ATF3可能是IgAN铁凋亡过程中的关键基因,并且可能与免疫细胞浸润有关。
Aims: Exploring key genes and potential molecular pathways of ferroptosis in immunoglobulin A nephropathy (IgAN). Methods: The IgAN datasets and ferroptosis-related genes (FRGs) were obtained in the Gene Expression Omnibus (GEO) and FerrDb database. Differentially expressed genes (DEGs) were identified using R software and intersected with FRGs to obtain differentially expressed FRGs (DE-FRGs). After that, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis (PEA) and Gene Ontology (GO) functional annotation were performed on DE-FRGs. In the Search Tool for the Retrieval of Interacting Genes (STRING) website, we construct a protein-protein interaction (PPI) network. The PPI network was further investigated with screening hub genes with Cytoscape software. The core genes were then subjected to gene set enrichment analysis (GSEA). Finally, the samples were analyzed for immune infiltration in R, and the correlation between hub genes and immune cells was analyzed. Results: A total of 347 DEGs were identified. CD44, CDO1, CYBB, IL1B, RRM2, AKR1C1, activated transcription factor-3 (ATF3), CDKN1A, GDF15,
JUN, MGST1, MIOX, MT1G, NR4A1, PDK4, TNFAIP3, and ZFP36 were determined as DE-FRGs.
JUN, IL1B, and ATF3 were then screened as hub genes. GSEA and immune infiltration analysis revealed that the hub genes were closely associated with immune inflammatory responses such as NOD-like receptor signaling, IL-17 signaling, and TNF signaling. Conclusions: Our results show that
JUN and ATF3 are possibly critical genes in the process of IgAN ferroptosis and may be related with immune cell infiltration.