血浆miR-181b和miR-194作为急性移植物抗宿主病诊断及疗效评价的标志物的研究

Plasma MiR-181b and MiR-194 as Biomarkers for Acute Graft-Versus-Host Disease and Significance of Their Changes

目的:研究血浆中miR-181b和miR-194的水平变化与异基因造血干细胞移植后发生急性移植物抗宿主病(aGVHD)的关联性,确定新的aGVHD诊断及预测标志物。方法:采用qRT-PCR方法检测31例接受异基因造血干细胞移植的患者移植前、移植后15 d以及发生aGVHD时血浆中miR-181b和miR-194表达水平变化,利用ROC曲线及曲线下面积分析移植后第15天miR-181b和miR-194的表达量作为aGVHD早期诊断标志物的特异性和敏感性。结果:发生aGVHD时患者血浆miR-181b和miR-194表达水平较移植前显著上调(P <0.05),且在治疗后表达水平下调,与移植前水平相比无显著差异。移植后第15天,aGVHD组miR-181b和miR-194的表达水平较未发生aGVHD组显著上调(P <0.05),且表达水平增高先于临床诊断。该检测时间点miR-181b诊断aGVHD曲线下面积0.91±0.05(特异性为0.94,敏感性为0.69),miR-194诊断aGVHD曲线下面积0.91±0.06(特异性为0.94,敏感性为0.77)。结论:miR-181b和miR-194的表达量可作为aGVHD早期诊断及疗效评价的特异性标志物。

Objective:To investigate the clinical correlation of expression level changes of miR-181 b and miR-194 to the pathogenesis of acute graft-versus-host disease(aGVHD),and determine plasma miR-181 b and miR-194 as the potential bio markers for aGVHD.Methods:The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT) at before HSCT,15 days after HSC.T and onset of aGVHD.The expression levels of miR-181 b and miR-194 were detected by quantitative real-time PCR.Receiveroperating characteristic(ROC) curves and the area under the ROC curve(AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD.Results:MiR-181 b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD(P <0.05),and there was no significant difference in comparison with the level of before HSCT(P>0.05).The expressions of plasma miR-181 b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with nonGVHD patients(P <0.05).Moreover,these elevated miRNAs were detected before aGVHD.The AUC of miR-181 b predicting aGVHD was 0.91±0.05(specificity was 0.94,sensitivity was 0.69).The AUC of miR-194 predicting aGVHD was 0.91±0.06(specificity was 0.94,sensitivity was 0.77).Conclusion:MiR-181 b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.