Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine
Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine
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DOI：
10.1016/j.euf.2017.02.018
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发表时间：
2018-12-01
影响因子：
5.4
通讯作者：
Sorensen, Karina D.
中科院分区：
文献类型：
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作者：
Fredsoe, Jacob;Rasmussen, Anne K. I.;Sorensen, Karina D.
背景资料：前列腺特异性抗原（PSA）检测在前列腺癌（PC）检测中的广泛应用导致了广泛的过度诊断和过度治疗。尿中microRNA（microRNA，miRNA）生物标志物在前列腺癌的诊断和预后中可能是有用的。目的：训练和验证尿中microRNA（microRNA，miRNA）生物标志物，以帮助前列腺癌的诊断和预后。我们通过逆转录-聚合酶链反应分析了29例良性前列腺增生（BPH）患者无细胞尿液样本中92种miRNAs的表达水平和215例临床局限性PC患者（队列1）。我们的研究结果在29例BPH患者和220例临床局限性PC患者的独立队列中得到验证（队列2）。结果和局限性：我们在PC患者的尿液样本中鉴定并验证了几种失调的miRNA。此外，我们训练了一种新的诊断性三miRNA模型（miR-222 - 3p * miR-24 - 3p/miR-30 c-5p），该模型在队列1中以0.95的曲线下面积（AUC）区分BPH和PC患者，并在队列2中成功验证（AUC 0.89）。此外，我们训练了一个新的预后三miRNA模型，（miR-125 b-5p * let-7a-5p/miR-151 - 5p）预测根治性乳腺癌切除术后生化复发时间，在队列1中独立于常规临床病理参数，并在队列2中成功验证。我们的新型诊断和预后三miRNA标签的未来临床应用可能有助于PC的初步诊断和指导治疗决策。患者总结：我们使用两个大的患者队列，在尿液中寻找新的前列腺癌生物标志物。我们在尿液中发现了两组新的microRNA生物标志物，可以准确预测前列腺癌的存在和前列腺切除术后复发的可能性。在开发实际的临床试验之前，还需要进一步的研究。(C)2017年欧洲泌尿外科协会。由爱思唯尔公司出版
Background: Widespread use of prostate-specific antigen (PSA) testing for prostate cancer (PC) detection has led to extensive overdiagnosis and overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC diagnosis and prognosis.Objective: To train and validate urine-based microRNA (miRNA) biomarkers that may assist in PC diagnosis and prognosis.Design setting, and partcipants: We profiled the expression levels of 92 miRNAs via reverse transcriptase-poymerase chain reaction in cell-free urine samples from 29 patients with benign prostatic hyperplasia (BPH) and 215 patients with clinically localized PC (cohort 1). Our findings were validated in an independent cohort of 29 BPH patients and 220 patients with clinically localized PC (cohort 2).Result and limitations: We identified and validated several deregulated miRNAs in urine samples from PC patients. In addition, we trained a novel diagnostic three-miRNA model (miR-222-3p*miR-24-3p/miR-30c-5p) that distinguished BPH and PC patients with an area under the curve (AUC) of 0.95 in cohort 1, and was successfully validated in cohort 2 (AUC 0.89). Furthermore, we trained a novel prognostic three-miRNA model (miR-125b-5p*let-7a-5p/miR-151-5p) that predicted time to biochemical recurrence after radical prostatectomy independently of routine clinicopathological parameters in cohort 1, and was successfully validated in cohort 2.Conclusions: Future clinical implementation of our novel diagnostic and prognostic three-miRNA signatures could help in primary diagnosis of PC and guide treatment decisions. Further validation studies are warranted.Patient summary: Using two large patient cohorts, we searched for novel prostate cancer biomarkers in urine. We found two new sets of microRNA biomarkers in urine that could accurately predict the presence of prostate cancer and the likelihood of recurrence after prostatectomy. Further studies are needed before an actual clinical test can be developed. (C) 2017 European Association of Urology. Published by Elsevier B.V.