急性缺血性卒中患者血清miRNA-148a表达水平检测及其临床价值预探索

Clinical Value and Expression Level of Serum miRNA-148a in Patients with Acute Ischemic Stroke

目的探讨急性缺血性卒中(acuteischemicstroke,AIS)患者血清miRNA-148a的表达水平及其临床价值。方法收集42例AIS患者和42例健康者的外周血血清样本,采用实时定量聚合酶链反应技术测定miRNA-148a的表达水平。绘制miRNA-148a对AIS诊断的受试者工作特征(receiver operating characteristic,ROC)曲线,并分析miRNA-148a与临床资料的相关性。从基因表达综合数据库下载GSE55937数据集对AIS患者的miRNA-148a水平进行进一步验证,并采用生物信息学方法预测其靶基因及生物功能。结果 AIS患者发病12 h内的miRNA-148a相对表达量低于健康对照组(0.76±0.23 vs1.02±0.21,P<0.001)。miRNA-148a诊断AIS的ROC曲线下面积为0.79(95%CI 0.70~0.89,P<0.001)。Spearman相关性检验表明,miRNA-148a水平与AIS患者的脑梗死面积(r=-0.34,P=0.03)和hs-CRP水平(r=-0.43,P=0.005)负相关。在GSE55937数据集中,miRNA-148a相对表达量在AIS组也明显低于对照组(1.93±0.46 vs2.52±1.00,P=0.011),其对AIS诊断的ROC曲线下面积为0.69(95%CI0.54~0.84,P=0.022)。生物信息学方法共预测到58个miRNA-148a的靶基因,包括WNT10B、DNMT1等。这些靶基因主要涉及的分子机制包括调控细胞凋亡、Fox O信号通路、PI3K-Akt通路等。结论 AIS患者发病早期的血清miRNA-148a水平降低,可能涉及细胞凋亡和FoxO、PI3K-Akt等信号通路,提示miRNA-148a可能在AIS的诊断及病情评估方面具有一定参考价值。

Objective To investigate the level and clinical value of serum miRNA-148 a in patients with acute ischemic stroke(AIS).Methods The serum samples of peripheral blood from 42 AIS patients and 42 healthy control participants were collected, and the miRNA-148 a levels of all subjects were measured by a realtime fluorogenic quantitative PCR. The receiver operating characteristic(ROC) curve of miRNA-148 a for the diagnosis of AIS was plotted, and the correlation between miRNA-148 a expressioin level and clinical data were analyzed. The GSE55937 dataset were downloaded from Gene Expression Omnibus to measure the miRNA-148 a expression level in AIS patients, and the target genes and biological functions of miRNA-148 a were predicted using bioinformatics analysis.Results The miRNA-148 a expression level in AIS patients within 12 h after onset was significantly lower than that in healthy control group(0.76±0.23 vs 1.02±0.21, P<0.001).The area under the ROC curve of miRNA-148 a for the diagnosis of AIS was 0.79(95%CI 0.70-0.89, P<0.001). Spearman correlation test showed that the miRNA-148 a expression level in AIS patients were negatively associated with infarction size(r=-0.34, P=0.03) and high sensitivity C-reactive protein(hs-CRP)(r=-0.43, P=0.005). In GSE55937 dataset, the level of miRNA-148 a was also remarkably lower in AIS than that in control group(1.93±0.46 vs 2.52±1.00, P=0.011), and the area under the ROC curve of miRNA-148 a for the diagnosis of AIS was 0.69(95%CI 0.54-0.84, P=0.022). A total of 58 target genes were predicted by bioinformatics methods, such as WNT10 B and DNMT1. The molecular mechanism of the target genes mainly involve the regulation of cell apoptosis, FoxO signaling pathway and PI3 K-Akt pathway and etc.Conclusions The serum miRNA-148 a level is significantly decreased in the early phase of AIS patients, and the mechanism of miRNA-148 a in stroke may involve cell apoptosis, FoxO signal pathway and PI3 K-Akt signal pathway. miRNA-148 a may have certain value in the diagnosis and assessment of AIS.