Asklepios Klinik Altona, Hamburg, Germany.
2 Albertinen-Krankenhaus Hamburg, Hamburg, Germany.
J Clin Oncol. 2019 Jun 1;37(16):1412-1423. doi: 10.1200/JCO.18.01480. Epub 2019 Mar 15.
Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT.
In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase.
For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p.
The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.
先前的研究表明，与经典的睾丸生殖细胞肿瘤（GCT）标志物相比，血清 microRNA（miR）-371a-3p 水平（所谓的 M371 试验）具有更高的灵敏度和特异性，并且适用于精原细胞瘤和非精原细胞瘤。我们旨在证实该试验作为 GCT 新型生物标志物的有用性。
在一项前瞻性、多中心研究中，通过定量聚合酶链反应检测了 616 例 GCT 患者和 258 例男性对照的血清样本中的血清 miR-371a-3p 水平（miR 水平）。GCT 人群包括 359 例精原细胞瘤患者和 257 例非精原细胞瘤患者；371 例为临床 I 期疾病，201 例为全身性疾病，46 例为复发。424 例患者在睾丸切除术前后进行了配对测量；118 例全身性疾病患者在治疗期间进行了连续测量。将 miR 水平与β-人绒毛膜促性腺激素、α-胎蛋白和乳酸脱氢酶进行比较。
对于 GCT 的初步诊断，M371 试验的敏感性为 90.1%，特异性为 94.0%，在接受者操作特征分析中曲线下面积为 0.966，阳性预测值为 97.2%。在精原细胞瘤中，α-胎蛋白、β-人绒毛膜促性腺激素和乳酸脱氢酶的灵敏度均低于 50%，而非精原细胞瘤的灵敏度略高。miR 水平与临床分期、原发性肿瘤大小和治疗反应显著相关。复发患者的 miR 水平升高，随后在缓解时降至正常。畸胎瘤不表达 miR-371a-3p。
M371 试验的敏感性和特异性均大于 90%，优于 GCT 的经典标志物。除畸胎瘤外，所有组织学亚组均表达该标志物。在进一步验证后，该试验可考虑用于临床实施。
