类风湿关节炎患者血清外泌体长链非编码RNA Hotair和XIST的表达及意义

Expressions and clinical significance of LncRNA Hotair and XIST in serum-derived exosomes of patients with rheumatoid arthritis

目的 研究类风湿关节炎(RA)患者血清来源外泌体中长链非编码RNA (lncRNA)Hotair、XIST、H19和MALAT1的表达水平,分析与RA患者炎症参数的相关关系,探讨其对RA的临床诊断价值。方法 收集70例RA患者为疾病组,同期就诊的40例系统性红斑狼疮(SLE)患者为疾病对照组,40例体检健康者为健康对照组(HC)。收集3组研究对象血清并提取外泌体,通过纳米粒径追踪仪检测外泌体浓度,采用实时定量PCR(RT-qPCR)法检测外泌体中lncRNA Hotair、XIST、H19和MALAT1的表达水平。采用Spearman秩相关分析Hotair、XIST与RA患者红细胞沉降率(ESR)、C-反应蛋白(CRP)和疾病活动评分-28(DAS-28)的相关性。绘制ROC曲线分析Hotair、XIST对RA患者的诊断价值。结果 与健康对照组相比,RA组和SLE组外泌体浓度显著升高(P<0.05),RA组与SLE组之间无显著差异(P>0.05)。血清外泌体lncRNA H19和MALAT1表达水平在3组间差异无统计学意义(P>0.05);lncRNA Hotair和XIST在RA组表达水平较SLE组和健康对照组显著增加(P<0.001),并且两者的表达水平与RA患者ESR、CRP、DAS-28具有正相关关系(P<0.05),诊断RA的ROC曲线下面积(AUCROC)分别为0.84(95%CI=0.78~0.90,P<0.001)和0.76(95%CI=0.68~0.83,P<0.001)。结论 血清外泌体来源lncRNA Hotair和XIST在RA患者中表达显著性升高,与血清ESR、CRP、DAS-28存在正相关关系,提示外泌体来源LncRNAHotair和XIST可作为诊断RA的潜在生物学标志物。

Objective To investigate the expression levels of lncRNA Hotair,XIST,H19 and MALAT1 in serum-derived exosomes of the patients with rheumatoid arthritis,and analyze their correlation with inflammatory parameters to explore the clinical diagnostic value for RA.Methods A total of 70 RA patients were collected as the disease group,40 patients with systemic lupus erythematosus(SLE)during the same period as the disease control group,and 40 healthy people who underwent physical examination as the healthy control group.Their serum samples were collected and the exosomes were extracted from patients'serum.The concentration of exosomes was detected by nano particle diameter tracking instrument.The expression levels of IncRNA Hotair,XIST,HI9 and MALATI in serum-derived exosomes of each group were detected by RT-qPCR.Spearman correlation analysis was used to further analyze the correlation between the levels of Hotair,XIST and ESR,CRP,DAS-28 score of RA patients.The clinical diagnostic value of Hotair,XIST for RA were analyzed by ROC curve.Results Compared with the healthy control group,the concentration of serum-derived exosomes in RA patients was significantly higher than that in healthy control group(P<0.05),but there was no significant dfference between RA group and SLE group(P>0.05).Moreover,no obvious differences of the expression levels of IncRNA H19 and MALATI were found among the three groups(P>0.05).The expression levels of lncRNA Hotair and XIST in RA group were significantly higher than those in SLE group and HC control group(P<0.001).The expression levels of IncRNA Hotair and XIST were positively correlated with ESR,CRP and DAS-28 score in RA patients(P<0.05).The AUC^(ROC) of serum-derived exosomes lncRNA Hotair,XIST in diagnosing RA were 0.84(95%CI=0.78 to 0.90,P<0.001)and 0.76(95%CI=0.68 to 0.83,P<0.001).Conclusion The expression levels of serum-derived exosomes lncRNA Hotair and XIST were significantly increased in RA patients,which was positively correlated with ESR,CRP and Das-28.These results suggested that serum-derived exosomes lncRNA Hotair and Xist may be used as potential biomarkers for RA diagnosis.