Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
Clin Genitourin Cancer. 2021 Dec;19(6):469-479. doi: 10.1016/j.clgc.2021.08.006. Epub 2021 Sep 15.
Circulating microRNAs have clear potential for improving malignant germ-cell-tumor (MGCT) diagnosis. Here, we address the central issue of whether measurement of a single microRNA is sufficient for detecting testicular MGCTs, or whether there is added benefit in quantifying other members of the 4-microRNA panel previously identified (miR-371a-3p/miR-372-3p/miR-373-3p and miR-367-3p).
We performed a pooled analysis of available published raw data where all 4 panel miRNAs had been assessed using pre-amplification PCR technology (4 studies; total 329 patients). Two studies using identical methodology (and identical normalization using endogenous miR-30b-5p) were used in the discovery phase (n = 51 patients: 17 MGCT, 34 controls). The 2 other studies (n = 278 patients: 140 MGCT, 138 controls), which assessed the same test panel but with different normalization approaches (endogenous miR-93-5p, exogenous cel-miR-39-3p), were used for the validation phase. We derived sensitivity, specificity, positive- and negative-predictive-values (PPV/NPV) for the detection thresholds that maximised the Youden Index (YI).
In the discovery-phase, the YI was 0.97 for miR-371a-3p (sensitivity = 1, specificity = 0.97), 0.71 (miR-367-3p), 0.68 (miR-372-3p), and 0.50 (miR-373-3p). These findings were confirmed in the validation-phase, with YI of 0.75 for miR-371a-3p (sensitivity = 0.90, specificity 0.85), 0.55 (miR-367-3p), 0.47 (miR-372-3p), and 0.51 (miR-373-3p). Importantly, no combination of markers added additional diagnostic benefit to miR-371a-3p alone, in either the discovery or the validation phase.
Quantifying circulating miR-371a-3p alone is sufficient for testicular MGCT diagnosis. PCR measurement of this single miRNA marker will be more cost-effective and easier to interpret, facilitating future incorporation into routine clinical practice.
循环 microRNAs 在提高恶性生殖细胞肿瘤（MGCT）诊断方面具有明显的潜力。在这里，我们研究了一个核心问题，即测量单个 microRNA 是否足以检测睾丸 MGCT，或者量化之前确定的 4 个 microRNA 面板中的其他成员（miR-371a-3p/miR-372-3p/miR-373-3p 和 miR-367-3p）是否会带来额外的益处。
我们对可用的已发表原始数据进行了汇总分析，其中使用预扩增 PCR 技术评估了所有 4 个面板 microRNA（4 项研究；共 329 名患者）。使用相同方法（并使用内源性 miR-30b-5p 进行相同的归一化）的 2 项研究用于发现阶段（n=51 例患者：17 例 MGCT，34 例对照）。另外 2 项研究（n=278 例患者：140 例 MGCT，138 例对照）评估了相同的测试面板，但采用不同的归一化方法（内源性 miR-93-5p，外源性 cel-miR-39-3p），用于验证阶段。我们为最大化 Youden 指数（YI）的检测阈值推导了敏感性、特异性、阳性和阴性预测值（PPV/NPV）。
在发现阶段，miR-371a-3p 的 YI 为 0.97（敏感性=1，特异性=0.97），miR-367-3p 为 0.71，miR-372-3p 为 0.68，miR-373-3p 为 0.50。这些发现在验证阶段得到了证实，miR-371a-3p 的 YI 为 0.75（敏感性=0.90，特异性 0.85），miR-367-3p 为 0.55，miR-372-3p 为 0.47，miR-373-3p 为 0.51。重要的是，在发现阶段或验证阶段，没有任何组合的标志物可以为 miR-371a-3p 单独检测增加额外的诊断益处。
定量检测循环 miR-371a-3p 足以用于睾丸 MGCT 的诊断。该单个 miRNA 标志物的 PCR 测量将更具成本效益，且更容易解释，这将有助于未来将其纳入常规临床实践。
