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.

Additional Metadata
Keywords CRIPTO, Fertility, Germ cell tumors, Germ cells, MiR-371a-3p, Semen, Serum, Testicular cancer
Persistent URL dx.doi.org/10.3390/cancers12030760, hdl.handle.net/1765/126086
Journal Cancers
Citation
Spiller, C.M, Lobo, J. (João), Boellaard, W.P.A, Gillis, A.J.M. (Ad 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). doi:10.3390/cancers12030760