肾细胞癌患者血清外泌体miR-181a-3p表达水平的临床价值

目的探讨肾细胞癌(renal cell carcinoma,RCC)患者血清外泌体微小核糖核酸-181a-3p(microRNA-181a-3p, miR-181a-3p)的表达变化,及其作为非侵入性辅助诊断RCC标志的临床价值。 方法收集2016年6月至2017年6月期间,南京总医院泌尿外科收治的未经治疗的79例RCC患者和75名年龄、性别匹配的健康体检者血清标本,分离血清外泌体并提取RNA。用实时荧光定量聚合酶链反应(quantitative real-time polymerase chai reaction,qRT-PCR)检测两组miR-181a-3p水平的2^-△Ct相对定量含量,并采用多种统计方法分析外泌体miR-181a-3p诊断RCC的效能。 结果qRT-PCR检测RCC患者血清外泌体miR-181a-3p的表达水平为0.264(0.095~0.782),较健康对照组[0.068(0.032~0.130)]明显上调(U=1022,P<0.001);同时,血清外泌体miR-181a-3p水平在早期(I/II期)RCC患者[0.202(0.105~0.543)]中也显著升高(U=699,P<0.001)。血清外泌体miR-181a-3p的受试者工作特征曲线(receiver operating characteristic curve,ROC)区分RCC与健康对照者的曲线下面积(AUC)为0.828(95%CI：0.765~0.890),敏感度为72.2%,特异度为72.0%;诊断I/II期RCC患者的AUC为0.837(95%CI：0.771~0.902),敏感度和特异度分别为75.4%和72.0%。经逻辑回归分析,血清外泌体miR-181a-3p是RCC的独立危险因素(OR=6.662,95%CI：3.294~13.474,P<0.001)。 结论RCC患者尤其早期患者血清外泌体miR-181a-3p显著升高,其可作为非侵入性辅助诊断RCC的新型分子标志。

The clinical value of serum exosomal miR-181a-3p levels in patients with renal cell carcinoma

ObjectiveTo investigated the expression of serum exosomal microRNA-181a-3p (miR-181a-3p) in patients with renal cell carcinoma (RCC) and to evaluate its clinical value as a noninvasive diagnostic marker for RCC. MethodsSeventy-nine RCC patients from Department of Urology and 75 age-sex matched healthy individuals from Health Checkup Center in Nanjing General Hospital between June 2016 and June 2017 were enrolled in this study. Serum exosome were isolated from the patients and healthy individuals, and the levels of exosomal miR-181a-3p were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical value of serum exosomal miR-181a-3p were further assessed by receiver operating characteristic curve (ROC) and logistics analyses. ResultsThe relative expression levels of serum exosomal miR-181a-3p in RCC patients [0.264 (0.095-0.782)] were significantly higher than those in healthy individuals [0.068 (0.032-0.130), U=1022, P<0.001]. Moreover, the levels of serum exosomal miR-181a-3p were also significantly higher in early stage RCC patients [0.202 (0.105-0.543)] than those in healthy individuals (U=699, P<0.001). Receive operating characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) for discriminating all RCC patients from healthy individuals was 0.828 (95%CI:0.765-0.890), and when at the optimal cutoff, the sensitivity was 72.2% and the specificity was 72.0%. The AUC for differentiating early stage RCC patients from healthy individuals was 0.837 (95%CI:0.771-0.902), with the sensitivity was 75.4% and the specificity was 72.0% when at the same cutoff. In addition, logistic regression analyses revealed that serum exosomal miR-181a-3p was an independent risk factor of RCC (odds ratio, OR=6.662, 95%CI:3.294-13.474, P<0.001). ConclusionSerum exosomal miR-181a-3p levels are significantly increased in RCC patients, especially the early patients, and may be served as a novel non-invasive auxiliary molecular diagnostic marker for RCC.