Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors
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Publication Date: | 2018 |
Other Authors: | , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/1822/58233 |
Summary: | 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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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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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