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Article

CRIPTO and miR-371a-3p Are Serum Biomarkers of Testicular Germ Cell Tumors and Are Detected in Seminal Plasma from Azoospermic Males

by
Cassy M. Spiller
1,†,
João Lobo
2,3,4,5,†,
Willem P. A. Boellaard
6,
Ad J. M. Gillis
2,
Josephine Bowles
1,‡ and
Leendert H. J. Looijenga
2,7,*,‡
1
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
2
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands
3
Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
4
Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
5
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal
6
Department of Urology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands
7
Department of Pathology, Lab. for Exp. Patho-Oncology (LEPO), Erasmus MC-University Medical Center Rotterdam, Cancer Institute, Be-432A, PO Box 2040, 3000 CA Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
†
Joint first authors.
‡
Joint senior authors.
Cancers 2020, 12(3), 760; https://doi.org/10.3390/cancers12030760
Submission received: 21 January 2020 / Revised: 10 March 2020 / Accepted: 20 March 2020 / Published: 23 March 2020
(This article belongs to the Collection Germ Cell Tumors)
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Abstract

miR-371a-3p is currently the most informative reported biomarker for germ cell tumors (GCTs). Another developmental-related biomarker, CRIPTO, is involved in the regulation of pluripotency and germ cell fate commitment. We aimed to assess the value of CRIPTO as a diagnostic and prognostic biomarker of testicular GCTs (TGCTs) and also to assess its presence in seminal plasma samples, compared with miR-371a-3p. In total, 217 and 94 serum/seminal plasma samples were analyzed. CRIPTO was quantified using ELISA and miR-371a-3p using bead-based isolation followed by RT-qPCR. Methylation profiling (EPIC array) for the CRIPTO promoter region was undertaken in 35 TGCT tissues plus four (T)GCT cell lines. Significantly higher CRIPTO concentration was found in sera of non-seminomas compared to controls (p = 0.0297), and in stage II/III disease compared to stage I (p = 0.0052, p = 0.0097). CRIPTO concentration was significantly positively correlated with miR-371a-3p levels in serum (r = 0.16) and seminal plasma (r = 0.40). CRIPTO/miR-371a-3p levels were significantly higher in seminal plasma controls when compared to serum controls (p = 0.0001, p < 0.0001). CRIPTO/miR-371a-3p were detected both in normospermic and azoospermic males, and levels were higher in TGCTs compared to GCNIS-only. We have provided the largest dataset of evaluation of CRIPTO in serum and seminal plasma of GCTs, showing its potential value as a biomarker of the disease.
Keywords: CRIPTO; fertility; germ cells; germ cell tumors; miR-371a-3p; semen; serum; testicular cancer CRIPTO; fertility; germ cells; germ cell tumors; miR-371a-3p; semen; serum; testicular cancer
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MDPI and ACS Style

Spiller, C.M.; Lobo, J.; Boellaard, W.P.A.; Gillis, A.J.M.; Bowles, J.; Looijenga, L.H.J. CRIPTO and miR-371a-3p Are Serum Biomarkers of Testicular Germ Cell Tumors and Are Detected in Seminal Plasma from Azoospermic Males. Cancers 2020, 12, 760. https://doi.org/10.3390/cancers12030760

AMA Style

Spiller CM, Lobo J, Boellaard WPA, Gillis AJM, Bowles J, Looijenga LHJ. CRIPTO and miR-371a-3p Are Serum Biomarkers of Testicular Germ Cell Tumors and Are Detected in Seminal Plasma from Azoospermic Males. Cancers. 2020; 12(3):760. https://doi.org/10.3390/cancers12030760

Chicago/Turabian Style

Spiller, Cassy M., João Lobo, Willem P. A. Boellaard, Ad J. M. Gillis, Josephine Bowles, and Leendert H. J. Looijenga. 2020. "CRIPTO and miR-371a-3p Are Serum Biomarkers of Testicular Germ Cell Tumors and Are Detected in Seminal Plasma from Azoospermic Males" Cancers 12, no. 3: 760. https://doi.org/10.3390/cancers12030760

APA Style

Spiller, C. M., Lobo, J., Boellaard, W. P. A., Gillis, A. J. M., Bowles, J., & Looijenga, L. H. J. (2020). CRIPTO and miR-371a-3p Are Serum Biomarkers of Testicular Germ Cell Tumors and Are Detected in Seminal Plasma from Azoospermic Males. Cancers, 12(3), 760. https://doi.org/10.3390/cancers12030760

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