Networks of pre-diagnostic circulating RNA in testicular germ cell tumour

Abstract Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed...

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Main Authors: Joshua Burton, Trine B. Rounge, Trine B. Haugen, Marcin W. Wojewodzic
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84484-z
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author Joshua Burton
Trine B. Rounge
Trine B. Haugen
Marcin W. Wojewodzic
author_facet Joshua Burton
Trine B. Rounge
Trine B. Haugen
Marcin W. Wojewodzic
author_sort Joshua Burton
collection DOAJ
description Abstract Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed Weighted Gene Co-expression Network Analysis (WGCNA) on mRNA and miRNA data from these samples. Central genes (hub genes) enriched functional pathways, and regulatory feature prediction were identified for all TGCT subtypes together and according to histology. The TGCT susceptibility genes TEX14, NARS2, and G3BP2, were identified as hub genes in both seminoma and non-seminoma networks. We also identified UBCA1, RCC1, FMR1, OAS3, and UBE2W as hub genes associated with TGCT. The genes OAS3 and UBE2W have previously been associated with testicular dysgenesis. Furthermore, network module analysis indicated transcription factors for oestrogen-related receptors to have a potential role during development of TGCT. The overlap between mRNA network hub genes and TGCT susceptibility genes indicates a common role in TGCT development.
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spelling doaj-art-01b8f11cd22043f681e6615d5f5255352025-01-19T12:17:51ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84484-zNetworks of pre-diagnostic circulating RNA in testicular germ cell tumourJoshua Burton0Trine B. Rounge1Trine B. Haugen2Marcin W. Wojewodzic3Department of Life Sciences and Health, OsloMet – Oslo Metropolitan UniversityDepartment of Pharmacy, University of OsloDepartment of Life Sciences and Health, OsloMet – Oslo Metropolitan UniversityDepartment of Research, Cancer Registry of Norway, Norwegian Institute of Public HealthAbstract Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed Weighted Gene Co-expression Network Analysis (WGCNA) on mRNA and miRNA data from these samples. Central genes (hub genes) enriched functional pathways, and regulatory feature prediction were identified for all TGCT subtypes together and according to histology. The TGCT susceptibility genes TEX14, NARS2, and G3BP2, were identified as hub genes in both seminoma and non-seminoma networks. We also identified UBCA1, RCC1, FMR1, OAS3, and UBE2W as hub genes associated with TGCT. The genes OAS3 and UBE2W have previously been associated with testicular dysgenesis. Furthermore, network module analysis indicated transcription factors for oestrogen-related receptors to have a potential role during development of TGCT. The overlap between mRNA network hub genes and TGCT susceptibility genes indicates a common role in TGCT development.https://doi.org/10.1038/s41598-024-84484-zNetwork analysisPre-diagnosticRNATesticular cancerTGCTWGCNA
spellingShingle Joshua Burton
Trine B. Rounge
Trine B. Haugen
Marcin W. Wojewodzic
Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
Scientific Reports
Network analysis
Pre-diagnostic
RNA
Testicular cancer
TGCT
WGCNA
title Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
title_full Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
title_fullStr Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
title_full_unstemmed Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
title_short Networks of pre-diagnostic circulating RNA in testicular germ cell tumour
title_sort networks of pre diagnostic circulating rna in testicular germ cell tumour
topic Network analysis
Pre-diagnostic
RNA
Testicular cancer
TGCT
WGCNA
url https://doi.org/10.1038/s41598-024-84484-z
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AT marcinwwojewodzic networksofprediagnosticcirculatingrnaintesticulargermcelltumour