Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors

Detalhes bibliográficos
Autor(a) principal: Pinto, F.
Data de Publicação: 2018
Outros Autores: Cárcano, F. M., da Silva, E. C. A., Vidal, D. O., Scapulatempo-Neto, C., Lopes, L. F., Reis, R. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/58233
Resumo: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well-characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis (p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high-risk testicular germ cell tumor patients.
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spelling Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumorsbiomarkersBrachyury proteinprognosistesticular neoplasmsCiências Médicas::Medicina BásicaScience & TechnologyThe T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well-characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis (p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high-risk testicular germ cell tumor patients.ICVS internal research funds, by the Portuguese FCT project (PTDC/SAU‐TOX/114549/2009‐FCOMP‐01‐0124‐FEDER‐016057) to Reis RM and Barretos Cancer Hospital Internal Research Fund. F. Pinto received a fellowship from FCT ref SFRH/BD/81369/2011 and SFRH/BPD/115730/2016). Project ON.2 SR&TD Integrated Program (NORTE‐07‐0124‐FEDER‐000017) cofinanced by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER)info:eu-repo/semantics/publishedVersionWileyUniversidade do MinhoPinto, F.Cárcano, F. M.da Silva, E. C. A.Vidal, D. O.Scapulatempo-Neto, C.Lopes, L. F.Reis, R. M.20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58233engPinto, F., Cárcano, F. M., da Silva, E. C. A., Vidal, D. O., Scapulatempo‐Neto, C., Lopes, L. F., & Reis, R. M. (2018). Brachyury oncogene is a prognostic factor in high‐risk testicular germ cell tumors. Andrology.2047-29192047-292710.1111/andr.1249529749711https://onlinelibrary.wiley.com/doi/full/10.1111/andr.12495info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:34:20Zoai:repositorium.sdum.uminho.pt:1822/58233Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:30:00.942065Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
title Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
spellingShingle Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
Pinto, F.
biomarkers
Brachyury protein
prognosis
testicular neoplasms
Ciências Médicas::Medicina Básica
Science & Technology
title_short Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
title_full Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
title_fullStr Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
title_full_unstemmed Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
title_sort Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
author Pinto, F.
author_facet Pinto, F.
Cárcano, F. M.
da Silva, E. C. A.
Vidal, D. O.
Scapulatempo-Neto, C.
Lopes, L. F.
Reis, R. M.
author_role author
author2 Cárcano, F. M.
da Silva, E. C. A.
Vidal, D. O.
Scapulatempo-Neto, C.
Lopes, L. F.
Reis, R. M.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Pinto, F.
Cárcano, F. M.
da Silva, E. C. A.
Vidal, D. O.
Scapulatempo-Neto, C.
Lopes, L. F.
Reis, R. M.
dc.subject.por.fl_str_mv biomarkers
Brachyury protein
prognosis
testicular neoplasms
Ciências Médicas::Medicina Básica
Science & Technology
topic biomarkers
Brachyury protein
prognosis
testicular neoplasms
Ciências Médicas::Medicina Básica
Science & Technology
description The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well-characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis (p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high-risk testicular germ cell tumor patients.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/58233
url http://hdl.handle.net/1822/58233
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Pinto, F., Cárcano, F. M., da Silva, E. C. A., Vidal, D. O., Scapulatempo‐Neto, C., Lopes, L. F., & Reis, R. M. (2018). Brachyury oncogene is a prognostic factor in high‐risk testicular germ cell tumors. Andrology.
2047-2919
2047-2927
10.1111/andr.12495
29749711
https://onlinelibrary.wiley.com/doi/full/10.1111/andr.12495
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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