阿尔茨海默病和血管性痴呆关键致病基因的筛选与鉴定  

Screening and identification of key pathogenic genes for Alzheimer’s disease and vascular dementia

作　　者：苏曦阳 尹安康 韩璐 王伟[2] 王娟[2] SU Xiyang;YIN Ankang;HAN Lu;WANG Wei;WANG Juan(Department of Laboratory Medicine,the Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310005,Zhejiang,China;Department of Laboratory Medicine,Tongde Hospital of Zhejiang Province,Hangzhou 310012,Zhejiang,China)

机构地区：[1]浙江中医药大学附属第二医院医学检验科,浙江杭州310005 [2]浙江省立同德医院医学检验科,浙江杭州310012

出　　处：《中国现代医生》2024年第26期9-14,共6页China Modern Doctor

摘　　要：目的利用生物信息学方法分析阿尔茨海默病(Alzheimer’s disease,AD)和血管性痴呆(vascular dementia,VD)与正常对照组的差异表达基因(differentially expressed genes,DEGs),筛选关键基因并验证它们与这两种痴呆的关系。方法从基因表达综合数据库(Gene Expression Omnibus,GEO)获取基因芯片数据集GSE122063,用GEO2R工具筛选AD、VD与正常对照组的DEGs,利用STRING数据库建立蛋白相互作用网络,使用Cytoscape筛选关键基因;利用DAVID数据库分析有网络连接的DEGs的基因本体(gene ontology,GO)富集和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路,预测DEGs的生物学功能;最后验证关键基因的表达,采用受试者操作特征曲线检测诊断效果。结果AD和VD组分别筛选出1099个和505个DEGs,其中69个在蛋白相互作用网络中有关联。根据GO分析,DEGs主要存在于细胞的外侧质膜、表面和质膜,它们通过影响信号传导、炎症应答等生物过程和具有受体结合、信号受体活性等功能,共同导致痴呆的发生。根据KEGG分析,DEGs在微生物感染、类风湿关节炎、系统性红斑狼疮、炎症性肠病等免疫相关信号通路中有显著富集。鉴定4个关键基因:CCR5、CCL2、FCGR2A和ITGB2,它们在AD和VD组中均有高表达,这些基因的曲线下面积表明它们可能对痴呆的诊断有价值。结论通过生物信息学方法分析AD和VD,发现富集的信号通路和关键基因与免疫和炎症有关。Objective This study utilizes bioinformatics methods to analyze differentially expressed genes(DEGs)between Alzheimer’s disease(AD)and vascular dementia(VD)compared to normal controls.The aim is to identify key genes and validate their relevance to both types of dementia.Methods Gene chip dataset GSE122063 were obtained from the Gene Expression Omnibus(GEO)database.Using the GEO2R tool,DEGs in AD,VD,and normal control group were screened.We constructed a protein-protein interaction network using the STRING database and identified key genes through Cytoscape.Subsequently,DAVID database were used to analyze gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways associated with interconnected DEGs,predicting their biological functions.Finally,diagnostic performance were validated and assessed by using receiver operating characteristic curves.Results In the AD and VD groups,we identified 1099 and 505 DEGs,respectively,with 69 genes showing associations in the protein-protein interaction network.GO analysis revealed that DEGs are primarily located in the extracellular matrix,cell surface,and plasma membrane.They influence biological processes such as signal transduction and inflammatory responses,with functions related to receptor binding and signal receptor activity,collectively contributing to dementia development.KEGG analysis indicated significant enrichment of DEGs in immune-related signaling pathways,including microbial infections,rheumatoid arthritis,systemic lupus erythematosus,and inflammatory bowel disease.Four key genes-CCR5,CCL2,FCGR2A,and ITGB2-with significantly elevated expression in both AD and VD groups were indentified.The area under the curve suggests their potential diagnostic value for dementia.Conclusion Through bioinformatics analysis of AD and VD,the enriched signaling pathways and key genes associated with immunity and inflammation were discovered.These findings may play a crucial role in dementia progression and provide new insights for early diagnosis.

关 键 词：阿尔茨海默病 血管性痴呆 生物信息学分析 差异表达基因 

分 类 号：R741.02[医药卫生—神经病学与精神病学]