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

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...

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Main Authors: Nina Mørup, Rytis Stakaitis, Ieva Golubickaite, Meritxell Riera, Marlene Danner Dalgaard, Mikkel H. Schierup, Niels Jørgensen, Gedske Daugaard, Anders Juul, Kristian Almstrup
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/10/2346
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author Nina Mørup
Rytis Stakaitis
Ieva Golubickaite
Meritxell Riera
Marlene Danner Dalgaard
Mikkel H. Schierup
Niels Jørgensen
Gedske Daugaard
Anders Juul
Kristian Almstrup
author_facet Nina Mørup
Rytis Stakaitis
Ieva Golubickaite
Meritxell Riera
Marlene Danner Dalgaard
Mikkel H. Schierup
Niels Jørgensen
Gedske Daugaard
Anders Juul
Kristian Almstrup
author_sort Nina Mørup
collection DOAJ
description 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 (<i>n</i> = 18), GCNIS-only (<i>n</i> = 5), and controls (<i>n</i> = 25) were sequenced. SP from men with TGCT/GCNIS (<i>n</i> = 37) and controls (<i>n</i> = 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 (<i>p</i> = 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.
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spelling doaj.art-fb2f37b52b36486894053288b8d117c82023-11-21T19:28:16ZengMDPI AGCancers2072-66942021-05-011310234610.3390/cancers13102346Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell TumorsNina Mørup0Rytis Stakaitis1Ieva Golubickaite2Meritxell Riera3Marlene Danner Dalgaard4Mikkel H. Schierup5Niels Jørgensen6Gedske Daugaard7Anders Juul8Kristian Almstrup9Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkBioinformatics Research Centre, Aarhus University, 8000 Aarhus C, DenmarkDTU Multi-Assay Core, Department of Health Technology, Technical University of Denmark, 2800 Lyngby, DenmarkBioinformatics Research Centre, Aarhus University, 8000 Aarhus C, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Oncology, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, DenmarkCirculating 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 (<i>n</i> = 18), GCNIS-only (<i>n</i> = 5), and controls (<i>n</i> = 25) were sequenced. SP from men with TGCT/GCNIS (<i>n</i> = 37) and controls (<i>n</i> = 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 (<i>p</i> = 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.https://www.mdpi.com/2072-6694/13/10/2346small RNAstesticular cancerdiagnostics
spellingShingle Nina Mørup
Rytis Stakaitis
Ieva Golubickaite
Meritxell Riera
Marlene Danner Dalgaard
Mikkel H. Schierup
Niels Jørgensen
Gedske Daugaard
Anders Juul
Kristian Almstrup
Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
Cancers
small RNAs
testicular cancer
diagnostics
title Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
title_full Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
title_fullStr Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
title_full_unstemmed Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
title_short Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors
title_sort small rnas in seminal plasma as novel biomarkers for germ cell tumors
topic small RNAs
testicular cancer
diagnostics
url https://www.mdpi.com/2072-6694/13/10/2346
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