miRNA-16、miRNA-146a、miRNA-223在类风湿关节炎患者外周血中检测的临床意义

Clinical significance of peripheral blood miRNA-16,miRNA-146a and miRNA-223 detection among patients with rheumatoid arthritis

目的研究miRNA-16、miRNA-146a、miRNA-223在类风湿关节炎(RA)患者外周血中的表达水平与健康人群的差异,探讨这3项指标的临床意义。方法收集68例RA确诊患者(RA组)及20例健康志愿者(健康对照组)的空腹静脉血,采用实时荧光定量PCR技术检测研究对象外周血中miRNA-16、miRNA-146a、miR-223的相对表达水平;比较RA患者与健康志愿者外周血中miRNA-16、miRNA-146a、miRNA-223的相对表达水平差异,Pearson分析RA患者血清这3项指标与类风湿因子(RF)、C反应蛋白(CRP)、DAS28评分的相关性;构建miRNA-16、miRNA-146a、miRNA-223的ROC曲线并计算曲线下面积(AUC),进而比较各指标单独及联合检测的灵敏度和特异度。结果 RA组患者外周血中miRNA-16、miRNA-146a、miRNA-223的相对表达水平显著高于健康对照组(P<0.05)。根据DAS28评分,进一步将RA患者分为缓解组和活动组,发现活动组患者外周血中miRNA-16、miRNA-146a、miRNA-223相对表达水平高于缓解组和健康对照组,差异均有统计学意义(P<0.05)。miRNA-16的表达水平与CRP、DAS28呈正相关(r=0.470、0.446,P<0.05),miRNA-146a的表达水平与CRP、DAS28呈正相关(r=0.408、0.407,P<0.05)。miRNA-223的表达水平与RF、CRP呈正相关(r=0.527、0.518,P<0.05)。miRNA-16、miRNA-146a、miRNA-223的AUC分别为0.63、0.75、0.89,灵敏度分别为68.70%、85.24%、87.63%,特异度分别为55.39%、63.57%、90.35%。三者联合使用作为RA标志物作ROC曲线,得到AUC为0.91,灵敏度为89.34%,特异度为91.56%。结论 miRNA-16、miRNA-146a、miRNA-223与RA发生、发展存在密切关系,联合检测具有更高的灵敏度和特异度,适用于临床早期诊断RA。

Objective To study the difference of expression levels of miRNA-16,miRNA-146 aand miRNA-223 in peripheral blood between the patients with rheumatoid arthritis(RA)and healthy population and to explore their clinical significance.Methods The fasting venous blood samples were collected from 68 patients definitely diagnosed as RA(RA group)and 20 healthy volunteers(HC group).The relative expression levels of peripheral blood miRNA-16,miRNA-146 aand miRNA-223 in the study subjects were detected by adopting RT-PCR.The differences in the relative expression levels of peripheral blood miRNA-16,miRNA-146 a,miRNA-223 were compared between the RA group and HC group.The correlation between three serum indexes with the rheumatoid factor(RF),DAS28 score and C-reactive protein(CRP)was analyzed by Pearson.The receiver operating characteristic(ROC)curves of miRNA-16,miRNA-146 aand miRNA-223 were constructed,and the area under the curve(AUC)was calculated,thus the sensitivity and specificity were compared among the single detection of each indicator and their combined detection.Results The relative expression levels of peripheral blood miRNA-16,miRNA-146 aand miRNA-223 in the RA group were significantly higher than those in the HC group,and the differences were statistically significant(P<0.05).The RA patients were further divided into the remission group and activity group according to the DAS28 scores.It was found that the relative expression levels of peripheral blood miRNA-16,miRNA-146 aand miRNA-223 in the activity group were higher than those in the remission group and HC group,and the difference was statistically significant(P<0.05).The expression level of miRNA-16 was positively correlated with CRP and DAS28(r=0.470,r=0.446,P<0.05),and the expression level of miRNA-146 awas positively correlated with CRP and DAS28(r=0.408,r=0.407,P<0.05).The expression level of miRNA-223 was positively correlated with RF and CRP(r=0.527,r=0.518,P<0.05).AUC of miRNA-16,miRNA-146 a,and miRNA-223 were 0.63,0.75,and 0.89 respectively,the sensitivities were 68.70%,85.24%and 87.63%respectively,and the specificities were 55.39%,63.57%and 90.35% respectively.The three indicators combined use served as the marker of RA,the ROC curve was drawn,the obtained AUC was 0.91,the sensitivity was 89.34%and the specificity was 91.56%.Conclusion miRNA-16,miRNA-146 a,and miRNA-223 have close relationship with the occurrence and development of RA.Their combined detection has higher sensitivity and specificity,which is suitable for clinically early diagnosis of RA.