Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Clin Chem. 2019 Apr;65(4):540-548. doi: 10.1373/clinchem.2018.296681. Epub 2019 Feb 6.
Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required.
Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis.
We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, (miR-222-3p*miR-24-3p/miR-30c-5p). High scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, predicted TRUS biopsy results with greater accuracy than PSA (AUC = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL).
We successfully validated a urine-based diagnostic 3-miRNA signature for PC () in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.
基于血清前列腺特异性抗原（PSA）检测检测前列腺癌（PC）会导致许多不必要的前列腺活检、过度诊断和对临床意义不大的肿瘤的过度治疗。因此，需要新的、更准确的分子生物标志物。
我们使用逆转录定量 PCR 测量了来自西班牙和丹麦的 4 个独立患者队列的细胞外囊泡富集的无细胞尿液样本中 45 个预选 microRNA（miRNA）的浓度，这些患者队列包括 758 例临床局限性 PC 患者、289 例良性前列腺增生（BPH）的非癌症对照者和 233 例因 PC 疑似而接受初始经直肠超声（TRUS）引导前列腺活检的患者（良性结果 101 例，恶性结果 132 例）。通过 ROC 和决策曲线分析评估诊断潜力。
我们在 PC 患者的尿液中发现并成功验证了 8 个上调和 21 个下调的 miRNA。此外，我们验证了先前鉴定的 3-miRNA 诊断比值模型， （miR-222-3p*miR-24-3p/miR-30c-5p）。在 3 个独立队列的 BPH 与 PC 患者的尿液样本中，高分提示为 PC（曲线下面积（AUC）= 0.84、0.71、0.72）。此外，与 PSA（AUC = 0.527）相比， 对诊断灰区（PSA≤10ng/ml）内的患者进行 TRUS 活检结果的预测更准确。
我们在来自 2 个国家的 3 个独立患者队列中成功验证了一种基于尿液的 PC 诊断 3-miRNA 特征（）。在未来，这种简单、非侵入性的检测可能会被用于帮助更准确地选择接受前列腺活检的患者。需要进行前瞻性临床验证。
