The accuracy of prostate-specific antigen or clinical examination in prostate cancer (PCa) screening is in question, and circulating microRNAs (miRNAs) can be alternatives to PCa diagnosis. However, recent circulating miRNA biomarkers either are identified upon small sample sizes or cannot have robust diagnostic performance in every aspect of performance indicators. These may decrease applicability of potential biomarkers for the early detection of PCa. We reviewed recent studies on blood-derived miRNAs for prostate cancer diagnosis and carried out a large case study to understand whether circulating miRNA pairs, rather than single circulating miRNAs, could contribute to a more robust diagnostic model to significantly improve PCa diagnosis. We used 1231 high-throughput miRNA-profiled serum samples from two cohorts to design and verify a model based on class separability miRNA pairs (cs-miRPs). The pairwise model was composed of five circulating miRNAs coupled to miR-5100 and miR-1290 (i.e. five miRNA pairs, 5-cs-miRPs), reaching approximately 99% diagnostic performance in almost all indicators (sensitivity = 98.96%, specificity = 100%, accuracy = 99.17%, PPV = 100%, NPV = 96.15%) shown by a test set (n = 484: PCa = 384, negative prostate biopsies = 100). The nearly 99% diagnostic performance was also verified by an additional validation set (n = 140: PCa = 40, healthy controls = 100). Overall, the 5-cs-miRP model had 1 false positive and 7 false negatives among the 1231 serum samples and was superior to a recent 2-miRNA model (so far the best for PCa diagnosis) with 18 false positives and 80 false negatives. The present large case study demonstrated that circulating miRNA pairs could potentially bring more benefits to PCa early diagnosis for clinical practice.

中文翻译：

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前列腺癌早期诊断：1231 份血清样本中的循环 microRNA 对可能超出单个 microRNA。

前列腺癌 (PCa) 筛查中前列腺特异性抗原或临床检查的准确性存在问题，循环 microRNA (miRNA) 可以替代 PCa 诊断。然而，最近的循环 miRNA 生物标志物要么是在小样本上鉴定的，要么在性能指标的各个方面都不能具有强大的诊断性能。这些可能会降低潜在生物标志物在 PCa 早期检测中的适用性。我们回顾了最近关于用于前列腺癌诊断的血液来源的 miRNA 的研究，并进行了一项大型案例研究，以了解循环 miRNA 对而不是单个循环 miRNA 是否有助于建立更强大的诊断模型以显着改善 PCa 诊断。我们使用来自两个队列的 1231 个高通量 miRNA 分析血清样本来设计和验证基于类可分离性 miRNA 对 (cs-miRPs) 的模型。成对模型由5个循环miRNAs偶联miR-5100和miR-1290组成（即5个miRNA对，5-cs-miRPs），在几乎所有指标上达到约99%的诊断性能（敏感性= 98.96%，特异性= 100 %，准确率 = 99.17%，PPV = 100%，NPV = 96.15%）由测试集（n  = 484：PCa = 384，阴性前列腺活检 = 100）。近 99% 的诊断性能也通过额外的验证集（n  = 140：PCa = 40，健康对照 = 100）进行了验证。总体而言，5-cs-miRP 模型在 1231 个血清样本中具有 1 个假阳性和 7 个假阴性，并且优于最近的 2-miRNA 模型（迄今为止最好的 PCa 诊断），具有 18 个假阳性和 80 个假阴性。目前的大型案例研究表明，循环 miRNA 对可能为临床实践的 PCa 早期诊断带来更多好处。