Zhu Lingping, Chen Tong, Ye Wenrui, Wang Jun-Yao, Zhou Ji-Peng, Li Zhen-Yu, Li Chuan-Chang
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
J Thorac Dis. 2019 May;11(5):1799-1808. doi: 10.21037/jtd.2019.05.24.
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.
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.
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.
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).
无保护左主干冠状动脉疾病（uLMCAD）患者因突发心力衰竭和急性心肌梗死而死亡率较高，因此迫切需要可靠的诊断生物标志物以早期检测该疾病。循环微RNA（miRNA）已成为一类用于心血管疾病的新型生物标志物。本研究的目的是探讨miRNA作为uLMCAD早期检测生物标志物的效用。
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。使用多变量逻辑回归的受试者工作特征（ROC）分析来单独和联合评估候选miRNA的诊断能力。
通过NGS发现miR-182-5p、miR-199a-5p和miR-5187-5p有显著差异表达（倍数变化分别为1.35、1.65、0.5，P值分别为0.018、0.046、0.030，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对照组n = 38），qPCR证实uLMCAD患者血浆中miR-182-5p的表达上调（2.57倍，P = 0.011），miR-5187-5p的表达下调（0.47倍，P = 0.018）。多变量逻辑回归的ROC分析表明，miR-182和miR-5187的AUC评分分别为0.97和0.94，表明作为uLMCAD生物标志物具有较高的诊断能力。有趣的是，相关性分析表明这两种miRNA的表达相互独立。
这些结果表明，循环miR-182-5p和miR-5187-5p是uLMCAD合适的诊断生物标志物，两者都可能在有创诊断冠状动脉造影（CAG）之前为区分uLMCAD患者与非CAD人群提供诊断信息。
