血清外泌体来源的miRNAs在多发性骨髓瘤中的临床研究

Clinical Study of miRNAs Derived from Serum Exosomes in Multiple Myeloma

目的:研究血清外泌体来源的miR-21、miR-18a、miR-146a、Let-7b在多发性骨髓瘤(MM)患者中的表达水平及其在预后评估中的价值。方法:采用ExoQuick试剂盒提取57例MM患者和20例健康体检者血清外泌体,用RTq PCR检测血清外泌体中miR-21、miR-18a、miR-146a、Let-7b的相对表达水平,采用Spearman相关性分析研究miR-21、miR-18a、miR-146a、Let-7b表达水平与常规实验室指标之间的相关性,Kaplan-Meier生存曲线分析miR-21、miR-18a、miR-146a、Let-7b的表达水平与MM患者总体生存的关系。结果:MM患者血清外泌体来源的miR-21、miR-18a、Let-7b的表达水平均显著低于正常对照组(P<0.001),而miR-146a在两组之间的表达水平无显著性差异(P>0.05)。miR-21的表达水平与血清β_(2)-微球蛋白浓度呈较强的负相关(r=-0.830),而与血肌酐、校正血清钙、胱抑素C等呈较弱的负相关(r=-0.488,-0.282,-0.627);Let-7b、miR-18a的表达水平与校正血清钙、β_(2)-微球蛋白、胱抑素C浓度均呈较弱的负相关(r=-0.305,-0.362,-0.461;-0.317,-0.542,-0.434);miR-146a的表达水平与常规实验室指标均无显著相关性。miR-21、miR-18a、Let-7b低表达组的MM患者的总体生存率显著低于高表达组患者(P<0.05),而miR-146a的表达水平与MM患者的总体生存无显著相关性。结论:血清外泌体来源的miR-21、miR-18a、Let-7b在MM患者中存在异常低表达,且与MM患者的总体生存率下降存在关联。

Objective: To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a,and Let-7b derived from serum exosomes in patients with multiple myeloma(MM). Methods: Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RTqPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a,and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve. Results: The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group(P<0.001), while the expression level of miR-146a between the two groups was not significantly different(P>0.05). The expression level of miR-21 was strongly negatively correlated with serum β_(2)-microglobulin concentration(r=-0.830), and weakly negatively correlated with serum creatinine, corrected serum calcium, and cystatin C(r=-0.488,-0.282,-0.627). The expression levels of Let-7b and miR-18a were also weakly negatively correlated with the corrected serum calcium, β_(2)-microglobulin, and cystatin C concentration(r=-0.305,-0.362,-0.461;-0.317,-0.542,-0.434). However, there was no significant correlation between the expression level of miR-146a and routine laboratory parameters in MM patients. The overall survival rate of MM patients with low expression level of miR-21, miR-18a, and Let-7b significantly decreased compared with high expression level group(P<0.05), however, the expression level of miR-146a was not related to the overall survival rate. Conclusion:Aberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM,which are associated with a worse overall survival rate.