血管性痴呆补体成分5a受体和趋化因子C-C基序配体-2基因的识别及其表达意义  

Identification of the C5aR1 and CCL2 genes in vascular dementia based on bioinformatics analysis and its clinical significance

作　　者：盛开 朱彦[2] 于明[2] 徐宇浩[2] Sheng Kai;Zhu Yan;Yu Ming;Xu Yuhao(Jiangsu University,Zhenjiang 212013,China)

机构地区：[1]江苏大学,镇江212013 [2]江苏大学附属医院神经内科,镇江212001

出　　处：《中华老年医学杂志》2025年第1期27-33,共7页Chinese Journal of Geriatrics

基　　金：国家自然科学基金(82101431)。

摘　　要：目的基于生物信息学分析血管性痴呆(VaD)补体成分5a受体(C5aR1)和趋化因子C-C基序配体-2(CCL2)基因进行识别,并探索血清C5aR1和CCL2水平在VaD患者血清中的表达和临床意义。方法在基因表达综合数据库(GEO)中选取GSE122063数据集,筛选VaD患者和非痴呆患者在额叶、颞叶中变化一致差异性基因,应用Matascape数据库分析差异性基因的功能及通路,应用STRING网络和Cytoscape软件明确关键基因。病例对照研究,纳入2022年1—12月在江苏大学附属医院神经内科就诊的53例VaD患者为VaD组,50例非痴呆人群做对照组。收集2组的一般资料、蒙特利尔认知评估量表(MoCA)、简易智力状态检查量表(MMSE)评分和脑小血管病(CSVD)总负荷评分,酶联免疫吸附法检测2组血清C5aR1和CCL2表达。分析VaD组血清C5aR1和CCL2水平与MoCA评分、MMSE评分和CSVD总负荷评分的相关性。采用受试者工作特征(ROC)曲线分析血清C5aR1和CCL2水平对VaD的诊断价值。结果在GSE122063数据集中,与非痴呆患者相比,VaD组中额叶和颞叶同时上调的基因有43个,同时下调的基因有63个。将106个基因导入Cytoscape软件后通过cytoHubba插件中的Stress和Betweenness算法得到两个关键基因C5aR1和CCL2。VaD组血清C5aR1[(57.25±10.34)μg/L比(43.26±8.24)μg/L,t=7.607,P<0.001]、CCL2[(210.42±42.19)ng/L比(151.73±36.04)ng/L,t=7.570,P<0.001]水平均高于对照组。血清C5aR1、CCL2水平与MoCA评分均呈负相关(r=-0.691、-0.668,P<0.001),与MMSE评分均呈负相关(r=-0.736、-0.729,P<0.001),与CSVD总负荷评分均呈正相关(r=0.598、0.582,P<0.001)。血清C5aR1、CCL2水平诊断VaD的ROC曲线下面积为0.838和0.845。C5aR1和CCL2联合诊断VaD的ROC曲线下面积为0.896。结论血清C5aR1、CCL2水平在VaD患者血清中表达升高,与VaD患者的认知功能和CSVD总负荷密切相关,或可用于VaD患者的辅助诊断。Objective Based on bioinformatics analysis,this study aimed to identify the complement component 5a receptor 1(C5aR1)and chemokine C-C motif ligand-2(CCL2)genes in vascular dementia(VaD)and to explore the expression and clinical significance of serum C5aR1 and CCL2 levels in VaD patients.MethodsThe GSE122063 dataset was selected from the Gene Expression Omnibus(GEO)database to screen for consistently differentially expressed genes in the frontal and temporal lobes of VaD patients and non-dementia patients.The Matascape database was used to analyze the functions and pathways of differentially expressed genes,and the STRING network and Cytoscape software were used to identify key genes.In this case-control study,53 VaD patients seeking care at the Department of Neurology of the Affiliated Hospital of Jiangsu University between January 2022 and December 2022 were included in the VaD group,and 50 non-dementia individuals were included in the control group.General information,Montreal Cognitive Assessment(MoCA)scores,Mini-Mental State Examination(MMSE)scores,and scores of the total cerebral small vessel disease(CSVD)burden were collected for both groups,and serum C5aR1 and CCL2 expression was detected.The correlation of serum C5aR1 and CCL2 levels with MoCA scores,MMSE scores,and scores of the total CSVD burden in the VaD group was analyzed.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic value of serum C5aR1 and CCL2 levels in VaD.ResultsIn the GSE122063 dataset,compared with non-dementia patients,there were 43 upregulated genes and 63 downregulated genes simultaneously in the frontal and temporal lobes in the VaD group.After importing 106 genes into the Cytoscape software and using the Stress and Betweenness algorithms in the cytoHubba plugin,two key genes,C5aR1 and CCL2,were identified.Serum levels of C5aR1[(57.25±10.34)μg/L vs.(43.26±8.24)μg/L,t=7.607,P<0.001]and CCL2[(210.42±42.19)ng/L vs.(151.73±36.04)ng/L,t=7.570,P<0.001]in the VaD group were higher than those in the

关 键 词：血管性痴呆 生物信息学 补体成分5a受体 趋化因子C-C基序配体-2 

分 类 号：R74[医药卫生—神经病学与精神病学]