多机构联合分析表明，循环 miR-371a-3p 单独即可用于睾丸恶性生殖细胞肿瘤诊断。
A Multi-institutional Pooled Analysis Demonstrates That Circulating miR-371a-3p Alone is Sufficient for Testicular Malignant Germ Cell Tumor Diagnosis.
机构信息
Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
出版信息
Clin Genitourin Cancer. 2021 Dec;19(6):469-479. doi: 10.1016/j.clgc.2021.08.006. Epub 2021 Sep 15.
BACKGROUND
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).
PATIENTS AND METHODS
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).
RESULTS
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.
CONCLUSION
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.
背景
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。
患者和方法
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）。
结果
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。
结论
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。
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