PBMCs-Derived microRNA Signature as a Prethrombotic Status Discriminator in Stable Coronary Artery Disease
PBMCs-Derived microRNA Signature as a Prethrombotic Status Discriminator in Stable Coronary Artery Disease
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PBMC 衍生的 microRNA 特征作为稳定冠状动脉疾病的血栓前状态鉴别器
DOI：
10.1055/s-0039-1700518
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发表时间：
2020-01-01
影响因子：
6.7
通讯作者：
Shi, DaZhuo
中科院分区：
文献类型：
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作者：
Gao, Jie;Liu, Jia;Shi, DaZhuo
稳定性冠状动脉疾病（SCAD）患者的血栓前状态（PTS）增加冠状动脉血栓形成的风险。越来越多的证据表明，微核糖核酸（miRNAs）可能成为SCAD合并PTS患者的有希望的生物标志物。本研究旨在鉴定SCAD合并PTS患者的miRNA特征，并评估其诊断意义。在筛选阶段，通过芯片检测35例SCAD患者外周血单个核细胞（PBMCs）中32个表达不同的mirna (DEMs)，与5名健康对照者进行比较。然后进行mirna基因网络分析，并选择4个dem在79例SCAD患者和19例健康对照的独立队列中进行逆转录-定量实时聚合酶链反应（RT-qPCR）测试验证。与健康对照组相比，RT-qPCR检测证实芯片检测miR-34a-5p、miR-432-5p和miR-370-3p表达上调；而RT-qPCR检测到的miR-495-3p上调与微阵列检测到的miR-495-3p低表达并不一致。与非PTS组相比，PTS组只有miR-34a-5p和miR-495-3p显著上调（p < 0.01, p < 0.05）。受试者工作特征（ROC）分析显示，pbmcs衍生的miR-34a-5p和miR-495-3p可以区分PTS，其ROC曲线下面积（AUC）分别为0.780（置信区间[CI]95% = 0.673-0.866）和0.712（置信区间[CI]95% = 0.599-0.808）。miR-34a-5p联合纤维蛋白原（FIB， PTS的传统生物标志物）将AUC提高至0.885 (CI95% = 0.793-0.946)，与FIB相比具有更强的预测能力，综合判别提高0.201 （p < 0.01）。因此，miR-34a-5p与FIB的结合可能作为SCAD患者PTS鉴别的有效工具。
Abstract Prethrombotic status (PTS) in patients with stable coronary artery disease (SCAD) increases the risk of coronary thrombosis. Accumulating evidences have indicated that micro-ribonucleic acids (miRNAs) may serve as promising biomarkers for SCAD patients with PTS. The present study aimed to identify the miRNA signature in SCAD patients with PTS and evaluated their diagnostic significance. In the screening phase, 32 differently expressed miRNAs (DEMs) in peripheral blood mononuclear cells (PBMCs) were detected in 35 SCAD patients compared with 5 healthy controls by microarray. MiRNA-gene network analysis was then performed, and 4 DEMs were selected for validation with reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) test in an independent cohort comprising 79 SCAD patients and 19 healthy controls. Compared with healthy controls, RT-qPCR test verified the upregulations of miR-34a-5p, miR-432–5p, and miR-370–3p detected by microarray; while the upregulation of miR-495–3p measured by RT-qPCR was not consistent with its low expression detected by microarray. Only miR-34a-5p and miR-495–3p were significantly upregulated in the PTS group compared with the non-PTS group (p < 0.01, p < 0.05). Receiver-operating characteristic (ROC) analysis showed that PBMCs-derived miR-34a-5p and miR-495–3p may discriminate PTS with the areas under the ROC curve (AUC) of 0.780 (confidence interval [CI]95% = 0.673–0.866) and 0.712 (CI95% = 0.599–0.808), respectively. The combination of miR-34a-5p and fibrinogen (FIB, a traditional biomarker for PTS) improved AUC to 0.885 (CI95% = 0.793–0.946) and showed added predictive ability compared with FIB, with an integrated discrimination improvement of 0.201 (p < 0.01). Therefore, the combination of miR-34a-5p and FIB may serve as an efficient tool for distinguishing PTS in SCAD patients.