Identification of Key Genes and Potential Therapeutic Drugs Associated with Microglial Senescence and Alzheimer's Disease Based on GEO Database Analysis
10.3969/j.issn.1671-7414.2025.06.002
- VernacularTitle:基于GEO数据库分析筛选小胶质细胞衰老与阿尔茨海默病相关的关键基因及潜在治疗药物
- Author:
Shuo GAO
1
;
Peichang WANG
1
;
Yuli HOU
1
Author Information
1. 首都医科大学宣武医院检验科,北京 100053
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
microglia;
senescence;
differential expressed genes;
bioinformatics
- From:
Journal of Modern Laboratory Medicine
2025;40(6):7-11,17
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify key genes and potential therapeutic drugs associated with Alzheimer's disease(AD)based on microglial senescence using bioinformatics analysis,providing new targets and insights for AD diagnosis and treatment.Methods Gene expression datasets related to microglial senescence and AD,specifically GSE62420 and GSE74615,were downloaded from the Gene Expression Omnibus(GEO)database.Differential Expressed Genes(DEGs)were identified using R software.Functional enrichment analysis,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,was performed using the DAVID online tool.The STRING database was used to construct the protein-protein interaction(PPI)network,and the CytoHubba plugin in Cytoscape software was applied to identify hub genes.The differential expression of hub genes was validated using the GSE129296 and GSE208386 datasets.Potential therapeutic drugs targeting these genes were predicted using the DSigDB database.Results A total of 35 DEGs,including 34 upregulated and 1 downregulated gene,were identified from the intersection of the GSE74615 and GSE62420 datasets.GO and KEGG enrichment analyses indicated that these DEGs were significantly involved in gene expression regulation,protein binding,metal ion binding,and the hypoxia-inducible factor 1(HIF-1)signaling pathway.PPI network analysis and CytoHubba screening identified ten hub genes:HIF1A,secreted phosphoprotein 1(SPP1),integrin alpha X(ITGAX),triggering receptor expressed on myeloid cells(TREM2),glycoprotein non-metastatic melanoma protein B(GPNMB),anexelekto receptor tyrosine kinase(AXL),Cystatin F(CST7),interleukin-12B(IL12B)、lipoprteinlipase(LPL)and fatty acid-binding protein 5(FABP5).Validation using the GSE129296 dataset showed that HIF1A,SPP1,ITGAX,TREM2,GPNMB,AXL,CST7 and FABP5 were significantly upregulated in microglia of AD mice,and the differences were statistically significant(t=8.411～29.49,all P<0.05).Further validation using the GSE208386 dataset indicated that LPL,SPP1,AXL and CST7 were significantly upregulated during microglial senescence,and the differences were statistically significant(t=4.755～5.964,all P<0.05).Based on these validation results,SPP1,AXL and CST7 were identified as key genes in AD.Drug prediction analysis using DSigDB revealed that potential therapeutic compounds targeting these genes exhibit anti-aging,anti-tumor,anti-inflammatory and DNA damage repair effects.Conclusion The key genes SPP1,AXL and CST7,identified based on microglial senescence,may serve as potential biomarkers for AD.Furthermore,multiple potential therapeutic drugs were predicted,offering new targets and strategies for AD diagnosis and treatment.
