Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study

TY - JOUR

T1 - Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study

AU - Dieckmann, Klaus-Peter

AU - Radtke, Arlo

AU - Geczi, Lajos

AU - Matthies, Cord

AU - Anheuser, Petra

AU - Eckardt, Ulrike

AU - Sommer, Jörg

AU - Zengerling, Friedemann

AU - Trenti, Emanuela

AU - Pichler, Renate

AU - Belz, Hanjo

AU - Zastrow, Stefan

AU - Winter, Alexander

AU - Melchior, Sebastian

AU - Hammel, Johannes

AU - Kranz, Jennifer

AU - Bolten, Marius

AU - Krege, Susanne

AU - Haben, Björn

AU - Loidl, Wolfgang

AU - Ruf, Christian Guido

AU - Heinzelbecker, Julia

AU - Heidenreich, Axel

AU - Cremers, Jann Frederik

AU - Oing, Christoph

AU - Hermanns, Thomas

AU - Fankhauser, Christian Daniel

AU - Gillessen, Silke

AU - Reichegger, Hermann

AU - Cathomas, Richard

AU - Pichler, Martin

AU - Hentrich, Marcus

AU - Eredics, Klaus

AU - Lorch, Anja

AU - Wülfing, Christian

AU - Peine, Sven

AU - Wosniok, Werner

AU - Bokemeyer, Carsten

AU - Belge, Gazanfer

PY - 2019/6/1

Y1 - 2019/6/1

N2 - PURPOSE: 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.PATIENTS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - PURPOSE: 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.PATIENTS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

U2 - 10.1200/JCO.18.01480

DO - 10.1200/JCO.18.01480

M3 - SCORING: Journal article

C2 - 30875280

VL - 37

SP - 1412

EP - 1423

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 16

ER -