胃癌患者血清外泌体中miRNA-21的表达及其临床意义

Expression of serum exosomal miRNA-21 and its clinical significance in gastric cancer

目的分析胃癌患者血清外泌体中miRNA-21的表达水平及其与患者临床病理学特征及预后的关系。方法利用外泌体试剂盒提取52例胃癌患者和10名健康人血清中的外泌体,并通过Western blot和纳米颗粒示踪法对其进行验证。采用RT-qPCR检测外泌体中miRNA-21的表达水平,分析其与胃癌患者临床病理学特征及预后的关系。结果胃癌患者血清外泌体中miRNA-21的表达水平较正常人明显升高(2.59±0.12比1.16±0.10,t=5.168,P<0.05),其高表达与肿瘤分化程度、浸润深度、淋巴结转移、远处转移、脉管浸润、神经侵犯及TNM分期均有关(均P<0.05)。外泌体miRNA-21高表达组胃癌患者的总生存期较低表达组胃癌患者短(χ^2=14.573,P<0.05)。多因素分析显示,血清外泌体中miRNA-21高表达是影响胃癌患者预后的独立因素(HR=2.863,95%CI:1.063~7.712,P=0.038)。结论胃癌患者血清外泌体中miRNA-21表达上调,并且其高表达与多种不良的临床病理因素及患者的不良预后有关。

Objective To explore the relationship of serum exosomal miRNA-21 expression and clinical pathological parameters and prognosis in gastric cancer(GC)patients.Methods Exosomes from serum samples of 52 GC patients and 10 healthy controls were extracted using the ExoQuick Exosome Precipitation Solution,and were further validated by immunoblotting for exosome markers and characterization of nanoparticle using NanoSight.The expression levels of exosomal miRNA-21 in exosomes was detected by RT-qPCR,and its relationship with clinicopathological features and prognosis was further analyzed.Results The expression level of miRNA-21 in serum exosomes of patients with GC was significantly higher than that of normal subjects(2.59±0.12 vs.1.16±0.10,t=5.168,P<0.05),and its high expression was significantly related to tumor grade,depth of invasion,lymph node metastasis,distant metastasis,vascular invasion,nerve invasion and TNM stage(all P<0.05).Patients in exosomal miRNA-21 high expression group had lower overall survival than that of exosomal miRNA-21 low expression group(χ^2=14.573,P<0.05).Multivariate analysis using the COX regression test identified that higher serum exosomal miRNA-21 was an independent predictor of mortality for GC patients(HR=2.863,95%CI:1.063-7.712,P=0.038).Conclusion The expression of miRNA-21 in serum exosomes of GC patients is up-regulated,and its high expression is associated with multiple unfavorable clinicopathological factors and poor prognosis of patients.