急性呼吸窘迫综合征新生儿血浆miR-6833-3p的表达水平及诊断效能  

Study of the expression and diagnostic effect of miR-6833-3p in neonatal acute respiratory distress syndrome

作　　者：吴越[1] 邱峰[2] WU Yue;QIU Feng(Neonatal Medical Centre,Children’s Hospital of Nanjing Medical University,Nanjing 210008;Cerebrovascular Disease Center,Nanjing Brain Hospital Affiliated to Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学附属儿童医院新生儿医疗中心,江苏南京210008 [2]南京医科大学附属脑科医院脑血管病救治中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2021年第11期1614-1619,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：南京市医学科技发展资金(QRX17086)。

摘　　要：目的:筛选并验证分析与新生儿急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)相关的微小核糖核酸(miRNA),初步研究患儿血浆中miR-6833-3p的表达水平及其诊断效能。方法:选取南京医科大学附属儿童医院25例ARDS患儿(ARDS组)为研究对象,同期选取32例普通新生儿为对照组。采用微流体芯片技术筛选与新生儿ARDS相关的miRNA,对于组间差异表达超过5倍的miRNA进一步进行实时荧光定量聚合酶链式反应(RT-PCR)验证芯片重复性及进行靶基因预测,对两组血浆miR-6833-3p的表达水平进行检测并与急性生理评分做相关性分析,通过绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析miR-6833-3p在患者中的诊断效能并计算诊断敏感度及特异度。结果:通过基因芯片筛选出24个与新生儿ARDS相关的高表达差异基因。表达差异超过5倍的miRNA有8个,4个上调的分别是miR-31-5p、miR-4754、miR-6833-3p和miR-192-3p,4个表达下调的基因分别是miR-362-3p、miR-11a、miR-7a-2-3p和miR-1382。通过验证发现miR-6833-3p在ARDS组血浆中显著上调(P<0.01),且与APACHEⅡ评分中的急性生理评分呈正相关(r=0.731,P<0.001)。通过靶基因预测分析发现miR-6833-3p与PI3-K/Akt、MAPK信号通路可能密切相关。相关ROC曲线结果也显示,miR-6833-3p预测新生儿ARDS的ROC曲线下面积为0.848,其诊断最佳阈值为1.03,约登指数最大值为0.59,此时miR-6833-3p的诊断灵敏度为84.55%,特异度为75.36%。结论:miR-6833-3p在新生儿ARDS血浆中的表达水平显著升高,可作为新生儿ARDS的特异性标志物。Objective:This study aims to screen and verify microRNA in neonatal acute respiratory distress syndrome(ARDS),preliminary study on miR-6833-3p level and its diagnostic effect in serum of ARDS neonate.Methods:Twenty-five infants with ARDS and 32 controls were investigated in this study.The miRNA microarray was utilized to explore the expression of miRNA in serum.Realtime PCR was used to verify the reproducibility of diagnostic chips and the miRNA target prediction on miRNAs that were over five folds differences between groups.Furthermore,correlation was conducted between levels of miR-6833-3p and APACHEⅡ scores.The diagnostic effect,sensitivity,and specificity were analyzed according to receiver operating characteristic(ROC)curve.Results:Twenty-four aberrant miRNAs were screened out as highly expressed,and among these miRNAs there were 8 miRNAs with over five folds differences of expression:miR-31-5p,miR-4754,miR-6833-3p and miR-192-3p were up-regulation;miR-362-3 p,miR-11 a,miR-7a-2-3p and miR-1382 were down-regulation.Through verification,it was found that the expression of miR-6833-3p in the plasma of the ARDS group was significantly up-regulated(P<0.01)and positively correlated with the acute physiological score in APACHEⅡ score(r=0.731,P<0.001).The miR-6833-3 p may be closely related to PI3-K/Akt and MAPK signaling pathways according to target gene prediction analysis.ROC curve showed that area under the curve was 0.848,with optimum threshold was 1.03,Youden’s index was0.59 with sensitivity of 84.55% and specificity of 75.36%.Conclusion:The miR-6833-3p was significantly raised in neonatal ARDS,and may has certain clinical diagnostic efficacy as a new biomarker of neonatal ARDS.

关 键 词：急性呼吸窘迫综合征 miR-6833-3p 诊断效能 新生儿 

分 类 号：R722.1[医药卫生—儿科]