Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation
Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation
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DOI：
10.1253/circj.cj-17-1194
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发表时间：
2018-04-01
影响因子：
3.3
通讯作者：
Sasano, Tetsuo
中科院分区：
文献类型：
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作者：
Natsume, Yu;Oaku, Kasumi;Sasano, Tetsuo
背景：最近的实验研究表明，在心房组织中表达的几个microRNAs(MiRNAs)促进了心房颤动(AF)的一种底物。然而，由于这些实验数据是否有助于确定循环中的miRNAs是否有助于确定循环中的miRNAs作为房颤的生物标志物，我们采用了人血清和小鼠心房样本的联合分析，目的是确定这些生物标志物用于预测房颤。方法和结果：从10例房颤患者和5名对照组的血清中筛选出733个miRNAs，从6个诱导性房性心动过速模型小鼠和3个对照组的心房组织中筛选出672个miRNAs。我们选择了在两个分析中都检测到表达的miRNAs，它们的表达水平在人类分析和/或小鼠分析中发生了变化。该筛选鉴定出11个候选miRNAs。接下来，我们使用定量RT-PCR对50名房颤和50名非房颤受试者中选择的miRNAs进行了量化。个体评估显示，4个miRNAs(miR-99a-5p、miR-192-5p、miR-214-3p和miR-342-5p)在房颤患者中显著上调。接收器-工作特性曲线表明，miR-214-3P和miR-342-5P的准确度最高。4种miRNAs联合应用可显著提高房颤的预测准确性(敏感性为76%，特异性为80%)。结论：房颤患者血清中存在新的循环miRNAs表达上调，可能成为房颤的潜在生物标志物。
Background: Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.Methods and Results: Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity).Conclusions: Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.