循环miR-126-3p在非小细胞肺癌中表达及诊断价值

Expression and diagnostic value of circulating miR-126-3p in non-small cell lung cancer

目的探讨循环微小核糖核酸(miR)-126-3p在非小细胞肺癌(NSCLC)中表达及诊断价值。方法收集多中心miR芯片及测序数据探讨NSCLC的循环miR-126-3p的表达差异。为了评估循环miR-126-3p综合表达水平,计算标准化均数差(SMD)和综合受试者工作特征(sROC)曲线,分析sROC曲线的曲线下面积(AUC),探讨灵敏度、特异度、阳性阴性似然比,并结合组织进一步综合分析循环miR-126-3p表达。通过miRDB、starBase v2.0和TargetScan 7.1,结合NSCLC中的上调差异基因,利用互补序列方法筛选了循环miR-126-3p潜在靶基因。结果基于6项循环miR数据集发现循环miR-126-3p表达水平高于对照组,差异有统计学意义(P<0.05),受试者工作曲线显示循环miR-126-3p有较强的诊断效能(AUC>0.5),而在199例NSCLC组中综合表达低于对照组(SMD=-1.46)。sROC曲线显示循环miR-126-3p区分NSCLC组和对照组有高准确性(AUC=0.91),Egger's检验不存在发表偏倚(P>0.05),灵敏度、特异度均≥0.80,阳性似然比、阴性似然比为5.37和0.18。此外,对26个数据集1320例NSCLC循环和组织综合分析显示,循环miR-126-3p在NSCLC组中表达低于对照组(SMD=-2.07)。sROC曲线显示低表达的循环miR-126-3p在区分NSCLC组和对照组有高准确性(AUC=0.97)。此外,筛选得到循环miR-126-3p的潜在靶基因ADAM9和SLC7A5在NSCLC组中表达均高于对照组。结论低表达的循环miR-126-3p可能是NSCLC高准确性筛查的重要生物标志物。

Objective To explore the expression and diagnostic value of circulating microRNA(miR)-126-3p in non-small cell lung cancer(NSCLC).Methods Multi-centred miR chips and sequencing data were collected to investigate the differential expression of circulating miR-126-3p in NSCLC.In order to evaluate the comprehensive expression level of circulating miR-126-3p in the cycle,the standardized mean difference(SMD)and summary receiver operating characteristic(sROC)curve were calculated,and the area under curve(AUC)of sROC curve was analyzed.Sensitivity,specificity,positive negative likelihood ratio were explored,and the expression of circulating miR-126-3p was further comprehensively analyzed in combination with tissue.By using miRDB,starBase v2.0,and TargetScan 7.1,combined with up-regulated differentially expressed genes in NSCLC,potential target genes of circulating miR-126-3p were screened using complementary sequence method.Results Based on six circulating miR datasets,the expression level of circulating miR-126-3p was higher than that of the control group,and the difference was statistically significant(P<0.05).The receiver operating characteristic curves showed that circulating miR-126-3p had strong diagnostic efficacy(AUC>0.5),and the comprehensive expression of circulating miR-126-3p was lower in 199 cases of NSCLC group than in the control group(SMD=-1.46).The sROC curve showed that circulating miR-126-3p distinguished the NSCLC group from the control group with high accuracy(AUC=0.91),Egger's test showed no publication bias(P>0.05),with sensitivity and specificity≥0.80,and positive likelihood ratio and negative likelihood ratio were 5.37 and 0.18,respectively.In addition,a comprehensive analysis of the circulation and tissue of 1320 NSCLC samples from 26 datasets showed that circulating miR-126-3p expression was lower in NSCLC group than in the control group(SMD=-2.07).The sROC curve showed that low-expression circulating miR-126-3p had high accuracy in distinguishing between the NSCLC group and the control group(AUC=0.97).In addition,potential target genes ADAM9 and SLC7A5 were screened for circulating miR-126-3p,and their expression in NSCLC group was higher than that in the control group.Conclusion Low expression of circulating miR-126-3p in the circulation may be an important biomarker for high-precision screening of NSCLC.