Circulating miR-182-5p and miR-5187-5p as biomarkers for the diagnosis of unprotected left main coronary artery 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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循环 miR-182-5p 和 miR-5187-5p 作为诊断无保护左主干冠状动脉疾病的生物标志物
DOI：
10.21037/jtd.2019.05.24
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发表时间：
2019-05-01
影响因子：
2.5
通讯作者：
Li, Chuan-Chang
中科院分区：
文献类型：
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作者：
Zhu, Lingping;Chen, Tong;Li, Chuan-Chang
背景资料：无保护左主干冠状动脉疾病（uLMCAD）患者因突发性心力衰竭和急性心肌梗死死亡率高，急需可靠的诊断生物标志物早期发现uLMCAD。循环microRNAs（microRNAs）已成为一类新型的心血管疾病生物标志物。本研究的目的是探讨miRNA作为早期检测uLMCAD的生物标志物的实用性。方法：最初采用高通量测序（NGS）比较uLMCAD患者与无冠状动脉疾病（CAD）患者的循环miRNA表达谱，以识别候选的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miRNAs的表达。采用多变量逻辑回归的受试者工作特征（ROC）分析来评估候选miRNAs单独和组合的诊断能力。通过NGS检测发现miR-182- 5 p、miR-199 a-5 p和miR-5187- 5 p的表达差异显著（倍数变化=1.35、1.65、0.5，P值分别=0.018、0.046、0.030，uLMCAD组和非CAD对照组均为n=5）。在更大的队列中（uLMCAD患者n=27，非CAD对照n=38），qPCR证实，在uLMCAD患者的血浆中，miR-182- 5 p的表达上调（2.57倍，P=0.011），miR-5187- 5 p的表达下调（0.47倍，P=0.018）。采用多变量逻辑回归的ROC分析显示，miR-182- 5 p和miR-5187- 5 p分别具有0.97和0.94的AUC评分，表明作为uLMCAD的生物标志物的高诊断能力。结论：循环miR-182- 5 p和miR-5187- 5 p是uLMCAD的合适的诊断生物标志物，两者都可能为uLMCAD患者和非CAD人群的有创诊断性冠状动脉造影（CAG）提供诊断信息。
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-182-5p and miR-5187-5p 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).