Department of Urology, Technische Universität Dresden, 01307 Dresden, Germany.
National Center for Tumor Diseases (NCT), 01307 Dresden, Germany.
Int J Mol Sci. 2020 May 27;21(11):3814. doi: 10.3390/ijms21113814.
Currently, voided urine cytology (VUC) serves as the gold standard for the detection of bladder cancer (BCa) in urine. Despite its high specificity, VUC has shortcomings in terms of sensitivity. Therefore, alternative biomarkers are being searched, which might overcome these disadvantages as a useful adjunct to VUC. The aim of this study was to evaluate the diagnostic potential of the urinary levels of selected microRNAs (miRs), which might represent such alternative biomarkers due to their BCa-specific expression. Expression levels of nine BCa-associated microRNAs (miR-21, -96, -125b, -126, -145, -183, -205, -210, -221) were assessed by quantitative PCR in urine sediments from 104 patients with primary BCa and 46 control subjects. Receiver operating characteristic (ROC) curve analyses revealed a diagnostic potential for miR-96, -125b, -126, -145, -183, and -221 with area under the curve (AUC) values between 0.605 and 0.772. The combination of the four best candidates resulted in sensitivity, specificity, positive and negative predictive values (NPV), and accuracy of 73.1%, 95.7%, 97.4%, 61.1%, and 80.0%, respectively. Combined with VUC, sensitivity and NPV could be increased by nearly 8%, each surpassing the performance of VUC alone. The present findings suggested a diagnostic potential of miR-125b, -145, -183, and -221 in combination with VUC for non-invasive detection of BCa in urine.
目前，尿液脱落细胞学（VUC）是检测尿液膀胱癌（BCa）的金标准。尽管它具有很高的特异性，但在灵敏度方面存在不足。因此，正在寻找替代生物标志物，它们可能作为 VUC 的有用辅助手段来克服这些缺点。本研究旨在评估选定 microRNAs（miRs）的尿液水平的诊断潜力，由于其在膀胱癌中的特异性表达，这些 microRNAs 可能代表此类替代生物标志物。通过定量 PCR 评估了 104 例原发性 BCa 患者和 46 例对照患者尿液沉淀物中 9 种 BCa 相关 microRNAs（miR-21、-96、-125b、-126、-145、-183、-205、-210、-221）的表达水平。受试者工作特征（ROC）曲线分析显示，miR-96、-125b、-126、-145、-183 和 -221 的诊断潜力，曲线下面积（AUC）值在 0.605 到 0.772 之间。四项最佳候选物的组合具有 73.1%、95.7%、97.4%、61.1%和 80.0%的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）和准确性。与 VUC 结合使用时，敏感性和 NPV 可分别提高近 8%，超过单独使用 VUC 的性能。这些发现表明，miR-125b、-145、-183 和 -221 与 VUC 联合使用具有诊断潜力，可用于非侵入性检测尿液中的 BCa。
