miR-30a-5p miR-206 miR-122-5pmiR-483-5p在新生儿呼吸窘迫综合征中的表达及临床意义

Expression and clinical significance of miR-30a-5p,miR-206,miR-122-5p,and miR-483-5p in neonatal respiratory distress syndrome

目的分析新生儿呼吸窘迫综合征(NRDS)中血清微小RNA(miRNAs)的表达变化,评估其对NRDS的诊断价值。方法选取福建医科大学附属第二医院新生儿重症监护室(NICU)住院80例NRDS新生儿(NRDS组)为对象,采用随机数字表法选取同期住院104例普通早产儿为对照组。2组选取质检合格总样本各12例,采用illuminaHiseq测序平台完成高通量测序,检测出NRDS组相对于正常组的表达差异miRNAs,筛选出组间差异表达超过9倍的miRNAs为候选miRNAs。选取NRDS组68例,对照组92例,采用实时荧光定量聚合酶链式反应(RT-qPCR)检测2组样本中候选miRNAs表达水平差异与芯片结果是否一致。绘制受试者工作特征(ROC)曲线分析其诊断效能。使用线性相关分析评估表达差异miRNAs与NRDS患儿呼吸机使用天数及住院天数相关关系。结果illuminaHiseq测序平台结果显示总计有119种差异表达的miRNA,共筛选出6种miRNAs作为候选标志物,分别是miR-30a-5p、miR-206、miR-370-3p、miR-122-5p、miR-483-5p和miR-193a-5p,miR-30a-5p、miR-206、miR-122-5p和miR-483-5p相对于对照组表达下降(P<0.01)。ROC曲线结果表明,血清miR-122-5p对诊断NRDS患儿的曲线下面积(AUC)为0.853,敏感度为88.2%,特异度为91.3%;血清miR-206对诊断NRDS患儿的AUC为0.798,敏感度为70.6%,特异度为89.6%;血清miR-30a-5p对诊断NRDS患儿的AUC为0.922,敏感度为87.6%,特异度为85.2%;血清miR-483-5p对诊断NRDS患儿的AUC为0.885,敏感度为76.5%,特异度为82.6%。相关关系结果表明,发现上述表达差异miRNAs对患儿呼吸机使用时间以及住院天数无相关。结论NRDS患儿血清中miR-30a-5p、miR-206、miR-122-5p和miR-483-5p表达相对普通早产儿具有差异性,可能是NRDS的潜在诊断标志物。

Objective To explore the expression changes of serum microRNAs(miRNAs)in neonatal respiratory distress syndrome(NRDS)and evaluate their diagnostic value in NRDS.Methods A total of 80 new-borns with NRDS(NRDS group)admitted to the NICU of the Second Hospital Affiliated to Fujian Medical Uni-versity were enrolled as the research subjects,and a total of 104 ordinary premature infants were selected as the control group using a random number table method.A total of 12 samples were selected from each of the two groups that passed the quality inspection for high-throughput sequencing using the illuminaHiseq sequencing platform.miRNAs with expression differences between NRDS and the normal group were detected,and miRNAs with more than 9-fold difference in expression between groups were selected as candidate miRNAs.A total of 68 cases in the NRDS group and 92 cases in the control group were selected to detect the difference in expression levels of candidate miRNAs in the two groups using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).ROC curves were plotted to analyze the diagnostic efficiency.Linear correlation analysis was used to assess the relationship between differentially expressed miRNAs and the duration of ventilator use and hospital stay in children with NRDS.Results The results from the Illumina HiSeq sequencing platform showed 119 dif-ferentially expressed miRNAs.A total of 6 miRNAs were selected as candidate biomarkers,namely miR-30a-5p,miR-206,miR-370-3p,miR-122-5p,miR-483-5p,and miR-193a-5p.Among them,miR-30a-5p,miR-206,miR-122-5p,and miR-483-5p exhibited decreased expression compared to the control group(P<0.01).The ROC curve results indicated that the serum miR-122-5p had an area under the curve(AUC)of 0.853 for diagnosing NRDS in infants,with a sensitivity of 88.2%and a specificity of 91.3%.The serum miR-206 had AUC of 0.798,with a sen-sitivity of 70.6%and a specificity of 89.6%.The serum miR-30a-5p had an AUC of 0.922,and a sensitivity of 87.6%,a specificity of 85.2%.The serum miR-483-5p had AUC of 0.885,with a sensitivity of 76.5%and a speci-ficity of 82.6%.The correlation analysis results indicated that the differential expression of the aforementioned miRNAs was not significantly correlated with the duration of mechanical ventilation and length of hospital stay in infants.Conclusion The expression of miR-30a-5p,miR-206,miR-122-5p,and miR-483-5p in the serum of children with NRDS is relatively different from that of ordinary premature infants,and may be a potential diag-nostic marker for NRDS.