Data_Sheet_1_Diagnostic value of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p in coronary artery disease-induced sudden cardiac death.docx

BackgroundThe identification of coronary artery disease-induced sudden cardiac death (CAD-SCD) has always been a medical challenge. MicroRNAs (miRNAs) played vital roles in pathogenesis processes and served as potential biomarkers for cardiovascular and many other diseases. The aim of this study was to investigate the diagnostic value of the specific miRNAs for CAD-SCD.
MethodsA total of 30 autopsy-verified CAD-SCD victims were selected, including 18 individuals who experienced more than once asymptomatic myocardial ischemia (CAD-activated SCD) and 12 victims without prominent pathological features of insufficient blood supply (CAD-silent SCD). Meanwhile, 30 traumatic victims were enrolled as controls. Systematic postmortem examinations were performed in all study population. The expressions of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).
ResultsRT-qPCR showed significant downregulations of miR-126-5p and miR-499a-5p in CAD-SCD victims, with no obvious difference in miR-134-5p. Receiver-operating characteristic analysis revealed the diagnostic performance of miR-126-5p (areas under the curve [AUC] = 0.76) and validated miR-499a-5p (AUC = 0.82) as a sensitive marker. Additionally, the decreased expression of the two specific cardio-miRNAs was detected for discriminating CAD-silent SCD and CAD-activated SCD. Compared with the limited diagnostic value of single miR-126-5p and miR-499a-5p, their combination could achieve better discriminative capacity (AUC = 0.82, sensitivity = 91.7%, specificity = 77.8%).
ConclusionCardiac miR-126-5p and miR-499a-5p presented good diagnostic abilities for CAD-SCD, and their combination could help evaluate CAD condition. These targeted miRNAs as novel biomarkers are expected to be useful to discriminate the detailed causes in real SCD cases.

背景 冠状动脉疾病相关性心源性猝死（coronary artery disease-induced sudden cardiac death, CAD-SCD）的鉴定始终是医学领域的一大难题。微小核糖核酸（microRNAs, miRNAs）在疾病发生发展进程中发挥关键调控作用，亦可作为心血管疾病及诸多其他疾病的潜在生物标志物。本研究旨在探讨特定miRNAs对CAD-SCD的诊断价值。
方法 本研究共纳入30例经尸检证实的CAD-SCD死者，其中18例曾发生过多次无症状心肌缺血（CAD-显性心源性猝死，CAD-activated SCD），12例无明显心肌供血不足病理特征（CAD-隐匿性心源性猝死，CAD-silent SCD）；同时纳入30例创伤性死亡者作为对照。对所有研究对象开展系统性尸检。采用实时定量聚合酶链反应（real-time quantitative polymerase chain reaction, RT-qPCR）检测分析心脏组织中miR-126-5p、miR-134-5p及miR-499a-5p的表达水平。
结果 实时定量PCR结果显示，CAD-SCD死者心脏组织中miR-126-5p与miR-499a-5p的表达显著下调，而miR-134-5p的表达无明显差异。受试者工作特征（receiver-operating characteristic, ROC）曲线分析表明，miR-126-5p（曲线下面积[areas under the curve, AUC] = 0.76）与经验证的miR-499a-5p（AUC = 0.82）均可作为灵敏的诊断标志物。此外，检测这两种特异性心脏miRNAs的表达下调情况，可用于区分CAD-隐匿性心源性猝死与CAD-显性心源性猝死。相较于单一miR-126-5p与miR-499a-5p有限的诊断价值，二者联合检测的判别能力更优（AUC = 0.82，灵敏度为91.7%，特异度为77.8%）。
结论 心脏组织中miR-126-5p与miR-499a-5p对CAD-SCD具有良好的诊断效能，二者联合检测有助于评估冠状动脉疾病病情。上述靶向miRNAs作为新型生物标志物，有望为实际心源性猝死病例的具体病因鉴别提供有效辅助手段。