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首页> 外文期刊>Journal of Thoracic Disease >Circulating miR-182-5p and miR-5187-5p as biomarkers for the diagnosis of unprotected left main coronary artery disease
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Circulating miR-182-5p and miR-5187-5p as biomarkers for the diagnosis of unprotected left main coronary artery disease

机译：循环miR-​​182-5p和miR-5187-5p作为生物标志物用于诊断未保护的左主冠状动脉疾病

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Background: Patients with unprotected left main coronary artery disease (uLMCAD) have high mortality rate due to sudden heart failure and acute myocardial infarction, for which reliable diagnostic biomarkers to detect this disease at an early stage are in urgent need. Circulating microRNAs (miRNAs) have emerged as a class of novel biomarkers for cardiovascular diseases. The purpose of this study was to investigate utility of miRNAs as biomarkers for early detection of uLMCAD. Methods: High-throughput sequencing (NGS) was initially employed to compare circulating miRNA expression profiles in uLMCAD patients to that in patients without coronary artery disease (CAD) to identify candidate miRNA biomarkers. We further validated the expression of candidate miRNAs by quantitative polymerase chain reaction (qPCR) in a larger cohort. Receiver operating characteristic (ROC) analysis with multivariate logistic regression was used to evaluate the diagnostic power of candidate miRNAs individually and combined. Results: MiR-182-5p, miR-199a-5p and miR-5187-5p were found significantly differentially expressed through NGS (fold changes =1.35, 1.65, 0.5, P values =0.018, 0.046, 0.030, respectively, n=5 for both uLMCAD group and non-CAD control group). In a larger cohort (n=27 for uLMCAD patient and n=38 for non-CAD controls), qPCR confirmed that expression of miR-182-5p was up-regulated (2.57-fold, P=0.011) and expression of miR-5187-5p was down-regulated (0.47-fold, P=0.018) in the plasma of uLMCAD patients. ROC analysis with multivariate logistic regression show that miR-182 and miR-5187 have an AUC score of 0.97 and 0.94 respectively, indicating high diagnostic power as biomarkers for uLMCAD. Interestingly, correlation analysis suggests that the expression of two miRNAs were independent to each other. Conclusions: These results suggested that circulating miR-182-5p and miR-5187-5p were suitable diagnostic biomarkers for uLMCAD, both potentially providing diagnostic information for discriminating uLMCAD patients from non-CAD population prior to invasive diagnostic coronary angiography (CAG).
机译：背景：患有未保护的左主冠状动脉疾病（uLMCAD）的患者由于突发性心力衰竭和急性心肌梗塞而具有很高的死亡率，因此迫切需要能够在早期发现该疾病的可靠诊断生物标志物。循环微RNA（miRNA）已成为心血管疾病的一类新型生物标记。这项研究的目的是调查miRNA作为uLMCAD早期检测的生物标记物的实用性。方法：最初采用高通量测序（NGS）比较uLMCAD患者和无冠心病（CAD）患者的循环miRNA表达谱，以鉴定候选miRNA生物标志物。我们通过定量聚合酶链反应（qPCR）在更大的队列中进一步验证了候选miRNA的表达。接受者操作特征（ROC）分析与多因素Logistic回归用于评估候选miRNA的诊断能力。结果：通过NGS，发现MiR-182-5p，miR-199a-5p和miR-5187-5p显着差异表达（倍数变化分别为1.35、1.65、0.5，P值分别为0.018、0.046、0.030，n = 5）。对于uLMCAD组和非CAD控件组）。在更大的队列中（uLMCAD患者为n = 27，非CAD对照为n = 38），qPCR证实miR-182-5p的表达上调（2.57倍，P = 0.011）和miR- uLMCAD患者血浆中的5187-5p被下调（0.47倍，P = 0.018）。具有多元逻辑回归的ROC分析显示，miR-182和miR-5187的AUC评分分别为0.97和0.94，表明其作为uLMCAD的生物标记物具有很高的诊断能力。有趣的是，相关分析表明，两个miRNA的表达彼此独立。结论：这些结果表明，循环的miR-182-5p和miR-5187-5p是uLMCAD的合适诊断生物标志物，都可能为在有创诊断冠状动脉造影（CAG）之前将uLMCAD患者与非CAD人群区分开提供诊断信息。

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