目前，前列腺癌（PCa）的检测基于前列腺特异性抗原（PSA）定量作为初始筛查，随后进行超声引导下经直肠活检。然而，假阴性活检的高发率通常导致不当的治疗。因此，新的分子生物标志物，如尿中的微小RNA（miRNAs），是重新定义PCa诊断的可能途径。在捷克玛萨里克纪念癌症研究所进行前列腺活检的356名患者（256例确认为前列腺癌，100例阴性前列腺活检），以及36名对照组受试者（健康对照组，良性前列腺增生症 - BPH）的尿样本被分为发现组和验证组进行分析。在发现阶段，使用QIAseq miRNA文库套件和NextSeq 500平台进行了小RNA测序。在独立验证阶段，通过RT-qPCR方法验证了鉴定到的miRNA候选者。使用小RNA测序方法，我们鉴定了12个尿液miRNAs在PCa患者和对照组之间明显异常。此外，独立验证显示了miR-501-3p和miR-335:miR-501比值区分PCa患者和阴性前列腺活检患者的能力。随后，将miR-335:miR-501比值与PSA和总前列腺体积（TPV）组合使用逻辑回归超过了单个参数的分析精度[曲线下面积（AUC）= 0.75，阳性预测值（PPV）= 0.85，阴性预测值（NPV）= 0.51]，并根据活检结果区分患者。将miR-335:miR-501比值与PSA和总前列腺体积组合能够识别阴性前列腺活检的患者，并有可能精简活检指征的决策制定。 版权所有 © 2023，国际抗癌研究所（George J. Delinasios博士），保留所有权利。

The detection of prostate cancer (PCa) is currently based on prostate-specific antigen (PSA) quantification as an initial screening followed by ultrasound-guided transrectal biopsy. However, the high rate of false-negative biopsies often leads to inappropriate treatment. Therefore, new molecular biomarkers, such as urine microRNAs (miRNAs), are a possible way to redefine PCa diagnostics.Urine samples of 356 patients undergoing prostate biopsy (256 cases with confirmed prostate cancer, 100 cases with negative prostate biopsy) at the Masaryk Memorial Cancer Institute (Czech Republic) and additional 36 control subjects (healthy controls, benign prostatic hyperplasia - BPH) were divided into the discovery and validation cohorts and analyzed. In the discovery phase, small RNA sequencing was performed using the QIAseq miRNA Library Kit and the NextSeq 500 platform. Identified miRNA candidates were validated by the RT-qPCR method in the independent validation phase.Using the small RNA sequencing method, we identified 12 urine miRNAs significantly dysregulated between PCa patients and controls. Furthermore, independent validation showed the ability of miR-501-3p and the quantitative miR-335:miR-501 ratio to distinguish between PCa patients and patients with negative prostate biopsy. The subsequent combination of the miR-335:miR-501 ratio with PSA and total prostate volume (TPV) using logistic regression exceeded the analytical accuracy of standalone parameters [area under curve (AUC)=0.75, positive predictive value (PPV)=0.85, negative predictive value (NPV)=0.51)] and discriminated patients according to biopsy outcome.Combination of miR-335:miR-501 ratio with PSA and total prostate volume was able to identify patients with negative prostate biopsy and could potentially streamline decision making for biopsy indication.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.