==inizio objective==

Testicular germ cell cancer (GCT) is one of the best curable malignancies with cure rates above 90% for clinical stage (CS) I and II and above 80% in the CS III [1].
Cornerstones of the clinical management are surgery, imaging technologies (sonography, computed tomography, magnetic resonance) and the measurement of the serum tumor markers alpha fetoprotein (AFP), beta-human chorionic gonadotropin ( eta-HCG) and lactate dehydrogenase (LDH) (2).
Utility of these classical tumor markers is limited due to the low sensitivity.
miRNAs are small noncoding RNAs which are part of the epigenetic regulation of gene expression (3). Dysregulation of miRNA expression is closely associated with cancer initiation, progression, and metastasis. During the last two decades, the involvement of miRNAs in various cancers and their role as potential biomarkers have been widely researched.
Recently, serum levels of miRNA-371a-3p have been shown to be a promising biomarker in the diagnosis of GCT by performing better than the conventional markers (4-7). The laboratory diagnostic M371-Test (mir|detect GmbH, Bremerhaven, Germany) is a high-quality test for real-time polymerase chain reaction (PCR) based detection of miRNA-371a-3p in human serum samples.
The aim of the study was to establish the M371-Test on the Thermocycler Rotor-Gene Q (Qiagen) platform and to evaluated the test under real life conditions in comparison to the classical markers AFP,beta-HCG and LDH.

==fine objective==

==inizio methodsresults==

After ethical committee approval, 96 M371 tests (23 first diagnosis, 73 follow up) were performed in 44 patients (median age 29 years) and compared with AFP, beta-HCG, LDH using histological diagnosis and/or CT scan and / or markers as gold standard.

==fine methodsresults==

==inizio results==

In patients with first diagnosis of TC, the M371-Test resulted positive in 73.7% analyses, AFP in 21%, LDH 31.6% and beta-HCG in 42.1%.
In patients who had a relapse under follow up for TC, the M371-Test resulted positive in 86.4% of analyses, AFP in 50%, LDH 31.8% and beta-HCG in 63.6%.
GCT/non seminoma lesions had a positive M371-Test in 83.3% of analyses, AFP in 77.8%, LDH in 38.9% and beta-HCG in 66.7% of the analyses, respectively. In GCT/ seminomas, the M371-Test was positive in 85% of analyses, AFP in 5%, LDH in 30% and beta-HCG in 50%, respectively.

==fine results==

==inizio discussions==

We evaluated the test under real life conditions. Real life conditions give insights in the quality of care of patients under everyday conditions, which most of the time cannot reproduce the same results as approval studies. In this study, in the group of patients with suspicion of TC, the M371-Test showed a sensitivity of 73.7% and a specificity of 75%, which is much lower than in Dieckmann et al.’s study [4].
Furthermore, more data are necessary to optimize the cut-off level for positivity in patients with suspicion and under follow-up of TC.

==fine discussions==

==inizio conclusion==

Under real life conditions and performed on the real-time Thermocycler Rotor-Gene Q (Qiagen) platform the M371 test shows a good performance a in comparison with the classical markers for detecting GCTs and in the follow up of patients after GCT, especially in seminomas.

==fine conclusion==

==inizio reference==

1.Rajpert-De Meyts E, McGlynn KA and Okamoto K: Testicular Germ Cell tumours. Lancet 387(10029): 1762-1774, 2016. PMID: 26651223. DOI: 10.1016/S0140-6736(15)00991-5
2.Belge G, Grobelny F, Radtke A, Bodes J, Matthies C, Wülfing C and Dieckmann KP: Serum levels of microRNA-371a-3p are not elevated in testicular tumours of non-germ cell origin. J Cancer Res Clin Oncol 147(2): 435-443, 2021. PMID: 33200255. DOI: 10.1007/s00432-020-03429-x
3. Li Z, Xu R and Li N: MicroRNAs from plants to animals, do they define a new messenger for communication? Nutr Metab (Lond) 1, 15: 68, 2018. PMID: 30302122. DOI: 10.1186/s12986-018-0305-8
4.Dieckmann KP, Radtke A, Geczi L, Zengerling F, Trenti E, Pichler R, Belz H, Zastrow S, Winter A, Melchior S, Hammel J, Kranz J, Bolten M, Krege S, Haben B, Loidl W, Ruf CG, Heinzelbecker J, Heidenreich A, Cremers JF, Oing C, Hermanns T, Fankhauser CD, Gillessen S, Reichegger H, Cathomas R, Pichler M, Hentrich M, Eredics K, Lorch A, Wülfing C, Peine S, Wosniok W, Bokemeyer C and 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 37(16): 1412-1423, 2019. PMID: 30875280. doi: 10.1200/JCO.18.01480.
5. Almstrup K, Lobo J, Morup N, Belge G, Rajpert-De Meyts E, Looijenga LHJ and Dieckmann KP. Application of miR- NAs in the diagnosis and monitoring of testicular germ cell tumours. Nat Rev Urol 17 (4): 201–213, 2020. PMID: 32157202. doi: 10.1038/s41585-020-0296-x.
6. Leão R, Albersen M, Looijenga LHJ, Tandstad T, Kollmannsberger C, Murray MJ, Culine S, Coleman N, Belge G, Hamilton RJ and Dieckmann KP. Circulating microRNAs, the next- generation serum biomarkers in testicular germ cell tumours: a systematic review. Eur Urol 80 (4): 456–466, 2021. PMID: 34175151. doi: 10.1016/j.eururo.2021.06.006.
7.Lobo J, Leão R, Gillis AJM, van den Berg A, Anson-Cartwright L, Atenafu EG, Kuhathaas K, Chung P, Hansen A, Bedard PL, Jewett MAS, Warde P, O’Malley M, Sweet J, Looijenga LHJ and Hamilton RJ.. Utility of serum miR-371a-3p in predicting relapse on surveillance in patients with clinical stage I testicular germ cell cancer. Eur Urol Oncol 4(3): 483-491, 2020. PMID: 33288479 DOI: 10.1016/j.euo.2020.11.004

==fine reference==