Small RNAs in seminal plasma as novel biomarkers for germ cell tumors

Nina Mørup; Rytis Stakaitis; Ieva Golubickaite; Meritxell Riera; Marlene Danner Dalgaard; Mikkel H. Schierup; Niels Jørgensen; Gedske Daugaard; Anders Juul; Kristian Almstrup

doi:10.3390/cancers13102346

Small RNAs in seminal plasma as novel biomarkers for germ cell tumors

Nina Mørup, Rytis Stakaitis, Ieva Golubickaite, Meritxell Riera, Marlene Danner Dalgaard, Mikkel H. Schierup, Niels Jørgensen, Gedske Daugaard, Anders Juul, Kristian Almstrup^*

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	2346
Journal	Cancers
Volume	13
Issue number	10
Number of pages	15
ISSN	2072-6694
DOIs	https://doi.org/10.3390/cancers13102346
Publication status	Published - 2021

Keywords

Diagnostics
Small RNAs
Testicular cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Small RNAs in seminal plasma as novel biomarkers for germ cell tumors",

abstract = "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.",

keywords = "Diagnostics, Small RNAs, Testicular cancer",

author = "Nina M{\o}rup and Rytis Stakaitis and Ieva Golubickaite and Meritxell Riera and Dalgaard, {Marlene Danner} and Schierup, {Mikkel H.} and Niels J{\o}rgensen and Gedske Daugaard and Anders Juul and Kristian Almstrup",

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year = "2021",

doi = "10.3390/cancers13102346",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

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TY - JOUR

T1 - Small RNAs in seminal plasma as novel biomarkers for germ cell tumors

AU - Mørup, Nina

AU - Stakaitis, Rytis

AU - Golubickaite, Ieva

AU - Riera, Meritxell

AU - Dalgaard, Marlene Danner

AU - Schierup, Mikkel H.

AU - Jørgensen, Niels

AU - Daugaard, Gedske

AU - Juul, Anders

AU - Almstrup, Kristian

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Diagnostics

KW - Small RNAs

KW - Testicular cancer

U2 - 10.3390/cancers13102346

DO - 10.3390/cancers13102346

M3 - Journal article

C2 - 34067956

AN - SCOPUS:85105740106

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 10

M1 - 2346

ER -

Small RNAs in seminal plasma as novel biomarkers for germ cell tumors

Abstract

Keywords

UN SDGs

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