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

Publication

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

Journal Paper/Review - Mar 15, 2019

Dieckmann Klaus-Peter, Heinzelbecker Julia, Heidenreich Axel, Cremers Jann Frederik, Oing Christoph, Hermanns Thomas, Fankhauser Christian Daniel, Gillessen Sommer Silke, Reichegger Hermann, Cathomas Richard, Pichler Martin, Hentrich Marcus, Eredics Klaus, Lorch Anja, Wülfing Christian, Peine Sven, Wosniok Werner, Bokemeyer Carsten, Ruf Christian Guido, Loidl Wolfgang, Haben Björn, Radtke Arlo, Geczi Lajos, Matthies Cord, Anheuser Petra, Eckardt Ulrike, Sommer Jörg, Zengerling Friedemann, Trenti Emanuela, Pichler Renate, Belz Hanjo, Zastrow Stefan, Winter Alexander, Melchior Sebastian, Hammel Johannes, Kranz Jennifer, Bolten Marius, Krege Susanne, Belge Gazanfer

Citation

Dieckmann K, Heinzelbecker J, Heidenreich A, Cremers J, Oing C, Hermanns T, Fankhauser C, Gillessen Sommer S, Reichegger H, Cathomas R, Pichler M, Hentrich M, Eredics K, Lorch A, Wülfing C, Peine S, Wosniok W, Bokemeyer C, Ruf C, Loidl W, Haben B, Radtke A, Geczi L, Matthies C, Anheuser P, Eckardt U, Sommer J, Zengerling F, Trenti E, Pichler R, Belz H, Zastrow S, Winter A, Melchior S, Hammel J, Kranz J, Bolten M, Krege S, Belge G. Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study. J Clin Oncol 2019; 37:1412-1423.

Type

Journal Paper/Review (English)

Journal

J Clin Oncol 2019; 37

Publication Date

Mar 15, 2019

Issn Electronic

1527-7755

Pages

1412-1423

Brief description/objective

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.