血清hsa-miR3173-5p和hsa-miR-4297作为心源性脑卒中诊断标志物的研究  

Serum hsa-miR3173-5p and hsa-miR-4297 as Diagnostic Markers of Cardiogenic Stroke

作　　者：刘旭阳 孙玉芳 汤舒洁 项涛 LIU Xuyang;SUN Yufang;TANG Shujie;XIANG Tao(Department of Emergency,The Affiliated Hospital of Southwest Jiaotong University,The Third People’s Hospital of Chengdu,Chengdu 610031,Sichuan,China)

机构地区：[1]西南交通大学附属医院成都市第三人民医院急诊科,四川成都610031

出　　处：《心血管病学进展》2024年第5期470-475,F0003,共7页Advances in Cardiovascular Diseases

基　　金：成都市卫健委科研课题(2021217)。

摘　　要：目的研究血清hsa-miR3173-5p和hsa-miR-4297与心源性脑卒中的关联性,及其作为诊断标志物的可行性。方法GEO数据库整合分析筛选出可能的心源性脑卒中特异性miRNA(hsa-miR3173-5p和hsa-miR-4297),通过孟德尔随机化与共定位分析验证两个miRNA对心源性脑卒中发病的危险作用,并对它们在miRNA-mRNA调控网络中的靶基因进行富集分析来寻找相关通路。纳入2022年3月—2023年1月于成都市第三人民医院急诊科诊断新发缺血性脑卒中的患者共103例,其中心源性脑卒中22例(病例组),非心源性脑卒中81例(对照组)。采用实时荧光定量聚合酶链反应检测血清hsa-miR3173-5p和hsa-miR-4297的表达水平,多因素逻辑回归分析其与心源性脑卒中的相关性,采用ROC曲线评估预测价值。结果孟德尔随机化分析提示遗传预测的循环血液中hsa-miR3173-5p和hsa-miR-4297表达增高分别使心源性脑卒中的发病风险增加46%和70%。共定位分析提示循环血液中hsa-miR3173-5p和hsa-miR-4297的表达与心源性脑卒中存在共享遗传变异的概率分别为95%和86%。病例组血清hsa-miR3173-5p和hsa-miR-4297表达水平显著高于对照组(P<0.05),hsa-miR3173-5p(OR=6.30,95%CI 1.79~22.14,P=0.004)和hsa-miR-4297(OR=12.38,95%CI 1.97~77.72,P=0.007)与心源性脑卒中有显著关联。hsa-miR3173-5p和hsa-miR-4297的ROC曲线下面积(AUC)分别为0.705和0.624,将hsa-miR3173-5p和hsa-miR-4297联合心房颤动共同进行分析,其AUC为0.842。结论hsa-miR3173-5p和hsa-miR-4297的表达水平与心源性脑卒中具有密切关联,有望作为心源性脑卒中的诊断标志物。Objective To explore the levels of serum hsa-miR3173-5p and hsa-miR-4297 and their feasibility as the diagnostic markers in cardiogenic stroke.Methods GEO database integration analysis screened out possible cardiogenic stroke-specific miRNAs(hsa-miR3173-5p and hsa-miR-4297),verified the risk role of the two miRNAs in the development of cardiogenic stroke by Mendelian randomization and colocalization analysis,and their target genes in the miRNA-mRNA regulatory network were enriched to search for related pathways.A total of 103 patients newly diagnosed with ischemic stroke in the emergency department from March 2022 to January 2023 were included,among which 22 cases were cardiogenic stroke(case group)and 81 were non-cardiogenic stroke(control group).The expression levels of serum hsa-miR3173-5p and hsa-miR-4297 were detected by real-time quantitative polymerase chain reaction,and their correlation with cardiogenic stroke was analyzed by multivariable logistic regression.The predictive value was evaluated using the receiver operating characteristic(ROC)curve.Results Mendelian randomization analysis suggested that genetically predicted increased expression of hsa-miR3173-5p and hsa-miR-4297 in circulating blood increased the risk of cardiogenic stroke by 46%and 70%respectively.Colocalization analysis suggested that the expression of hsa-miR3173-5p and hsa-miR-4297 in circulating blood has a 95%and 86%probability of shared genetic variation with cardiogenic stroke,respectively.The expression levels of serum hsa-miR3173-5p and hsa-miR-4297 in the case group were significantly higher than in the control group(P<0.05),and hsa-miR3173-5p(OR=6.30,95%CI 1.79~22.14,P=0.004)and hsa-miR-4297(OR=12.38,95%CI 1.97~77.72,P=0.007)were significantly associated with cardiogenic stroke.The area under the ROC curve(AUC)for hsa-miR3173-5p and hsa-miR-4297 were 0.705 and 0.624 respectively,and the AUC of the combined analysis of hsa-miR3173-5p and hsa-miR-4297 with atrial fibrillation is 0.842.Conclusion The expression levels of hsa-miR3

关 键 词：心源性脑卒中 MIRNA 诊断标志物 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R54[医药卫生—临床医学]