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Article

Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors

1
Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark
2
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital, 2100 Copenhagen, Denmark
3
Laboratory of Molecular Neurooncology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
4
Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania
5
Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C, Denmark
6
DTU Multi-Assay Core, Department of Health Technology, Technical University of Denmark, 2800 Lyngby, Denmark
7
Department of Oncology, Copenhagen University Hospital, 2100 Copenhagen, Denmark
8
Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Academic Editor: Kerstin Junker
Cancers 2021, 13(10), 2346; https://doi.org/10.3390/cancers13102346
Received: 13 April 2021 / Revised: 7 May 2021 / Accepted: 10 May 2021 / Published: 13 May 2021
Testicular cancer is the most common cancer among young men. It is rarely diagnosed at early stages, being only detected with a highly invasive procedure that presents notable side-effects. Circulating small RNAs have recently been identified as testicular tumor markers, but are unable to diagnose testicular cancer at an early pre-invasive stage. So far, studies have been limited to microRNAs, with other small RNAs remaining unexplored as likely biomarkers. By sequencing all small RNAs in semen samples from men with different stages of testicular cancer and healthy men, we identify signatures predictive of cancer, even at an early stage. Thus, our study provides great potential for non-invasive early diagnosis of testicular cancer. Extensive biological variance in small RNA levels across samples, together with small sample sizes, limit the power to detect single small RNA markers. Hence, larger studies are needed to confirm our findings and deduce their full diagnostic capacity.
Circulating miRNAs secreted by testicular germ cell tumors (TGCT) show great potential as novel non-invasive biomarkers for diagnosis of TGCT. Seminal plasma (SP) represents a biofluid closer to the primary site. Here, we investigate whether small RNAs in SP can be used to diagnose men with TGCTs or the precursor lesions, germ cell neoplasia in situ (GCNIS). Small RNAs isolated from SP from men with TGCTs (n = 18), GCNIS-only (n = 5), and controls (n = 25) were sequenced. SP from men with TGCT/GCNIS (n = 37) and controls (n = 22) were used for validation by RT-qPCR. In general, piRNAs were found at lower levels in SP from men with TGCTs. Ten small RNAs were found at significantly (q-value < 0.05) different levels in SP from men with TGCT/GCNIS than controls. Random forests classification identified sets of small RNAs that could detect either TGCT/GCNIS or GCNIS-only with an area under the curve of 0.98 and 1 in ROC analyses, respectively. RT-qPCR validated hsa-miR-6782-5p to be present at 2.3-fold lower levels (p = 0.02) in the SP from men with TGCTs compared with controls. Small RNAs in SP show potential as novel biomarkers for diagnosing men with TGCT/GCNIS but validation in larger cohorts is needed. View Full-Text
Keywords: small RNAs; testicular cancer; diagnostics small RNAs; testicular cancer; diagnostics
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MDPI and ACS Style

Mørup, N.; Stakaitis, R.; Golubickaite, I.; Riera, M.; Dalgaard, M.D.; Schierup, M.H.; Jørgensen, N.; Daugaard, G.; Juul, A.; Almstrup, K. Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors. Cancers 2021, 13, 2346. https://doi.org/10.3390/cancers13102346

AMA Style

Mørup N, Stakaitis R, Golubickaite I, Riera M, Dalgaard MD, Schierup MH, Jørgensen N, Daugaard G, Juul A, Almstrup K. Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors. Cancers. 2021; 13(10):2346. https://doi.org/10.3390/cancers13102346

Chicago/Turabian Style

Mørup, Nina, Rytis Stakaitis, Ieva Golubickaite, Meritxell Riera, Marlene D. Dalgaard, Mikkel H. Schierup, Niels Jørgensen, Gedske Daugaard, Anders Juul, and Kristian Almstrup. 2021. "Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors" Cancers 13, no. 10: 2346. https://doi.org/10.3390/cancers13102346

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