血浆外泌体hsa_circ_0001360对冠心病的诊断价值

Diagnostic value of blood exosome hsa_circ_0001360 in atherosclerosis

中文关键词: 冠心病  动脉粥样硬化  外泌体  环状核糖核酸

英文关键词: coronary heart disease  atherosclerosis  exosome  circular ribonucleic acid

中文摘要:

      目的 鉴别冠心病(CHD)患者血浆外泌体中异常表达的环状核糖核酸(circRNA),并确定其潜在的临床标志物价值.方法 从exoRBase数据库中获取CHD患者(n=6)和健康受试者(n=32)血液外泌体中的信使核糖核酸(mRNA)、circRNA和长链非编码RNA(lncRNA)表达数据.通过ENCORI和miRcode数据库预测mRNA、circRNA和lncRNA对应的微小RNA(miRNA).基于竞争性RNA调控机制建立circRNA/lncRNA-miRNA-mRNA相互作用网络.采用LASSO回归鉴别CHD患者特征性血液外泌体中的circRNAs,通过实时荧光定量PCR进行验证.结果 共鉴定出85个差异表达的cir-cRNA(4个表达上调,81个表达下调),43个差异表达的lncRNA(24个表达上调,19个表达下调),312个差异表达的基因(55个表达上调,257个表达下调).KEGG富集分析显示,差异基因主要与中性粒细胞胞外陷阱形成以及核苷酸结合寡聚化结构域样受体介导的信号通路相关.LASSO回归鉴定hsa_circ_0001360为CHD患者特征性血液外泌体circRNA,其表达量在CHD患者血浆外泌体中明显上升.受试者操作特征曲线显示,hsa_circ_0001360曲线下面积为0.880,灵敏度为90.00％,特异度为 90.00％,95％CI:0.706～1.000(P=0.004).结论 Hsa_circ_0001360 可能是 CHD 的重要诊断生物标志物,hsa_circ_0001360及其下游miRNA和mRNA相互作用网络可能有助于阐明动脉粥样硬化的发病机制.

英文摘要:

      Objective To identify abnormal expression of circular ribonucleic acid(circRNA)in plasma exosomes of pa-tients with coronary heart disease(CHD)and determine its potential clinical marker value.Methods The expression data of messenger ribonucleic acid(mRNA),circRNA and long non-coding RNA(lncRNA)in blood exosomes of CHD patients(n=6)and healthy subjects(n=32)were obtained from exoRBase database.The microRNA(miRNA)corresponding to mRNA,circRNA and lncRNA were predicted by ENCORI and miRcode databases.The circRNA/lncRNA-miRNA-mRNA interaction net-work was established based on the regulatory mechanism of competitive RNA.The circRNAs in the characteristic blood exosomes of CHD patients were identified by LASSO regression and verified by real-time fluorescent quantitative PCR.Results A total of 85 differentially expressed circRNAs(4 up-regulated and 81 down-regulated),43 differentially expressed lncRNAs(24 up-regula-ted and 19 down-regulated),and 312 differentially expressed genes(55 up-regulated and 257 down-regulated)were identified.KEGG enrichment analysis showed that the differentially expressed genes were mainly related to the formation of extracellular traps in neutrophils and signaling pathways mediated by nucleotide-binding oligomerization domain-like receptors.LASSO regres-sion identified hsa_circ_0001360 as a characteristic circRNA in the blood exosomes of CHD patients,and its expression level in-creased significantly in the plasma exosomes of CHD patients.The receiver operating characteristic curve showed that the area un-der the curve of the hsa_circ_0001360 was 0.880,the sensitivity was 90.00％,the specificity was 90.00％(95％CI:0.706-1.000,P=0.004).Conclusion Hsa_circ_0001360 may be an important diagnostic biomarker for CHD.Hsa_circ_0001360 and its downstream miRNA and mRNA interaction network may help elucidate the pathogenesis of atherosclerosis.