Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40589 |
Resumo: | Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness. |
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Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognosticationepigenetic biomarkershistone covalent modificationshistone methyltransferasesNO66Renal cell tumorsSMYD2SETD3Ciências Médicas::Ciências da SaúdeScience & TechnologyRenal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.This study was funded by research grants from Research Center of Portuguese Oncology Institute – Porto (CI-IPOP 4-2012) and European Community’s Seventh Framework Program – Grant number FP7-HEALTH-F5-2009-241783. ASP-L and FQV are and were supported by FCT-Fundação para a Ciência e a Tecnologia grants (SFRH/SINTD/94217/2013 and SFRH/ BD/70564/2010, respectively).Taylor and FrancisUniversidade do MinhoLuís, Ana Sílvia PiresCoimbra, Márcia VieiraVieira, Filipa QuintelaPinheiro, Pedro CostaSantos, Rui SilvaDias, Paula C.Antunes, LuísLobo, FranciscoOliveira, JorgeGonçalves, Céline SaraivaCosta, Bruno Filipe MarquesHenrique, RuiJerónimo, Carmen20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40589engPires-Luis, A. S., Vieira-Coimbra, M., Vieira, F. Q., Costa-Pinheiro, P., Silva-Santos, R., Dias, P. C., . . . Jeronimo, C. (2015). Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication. Epigenetics, 10(11), 1033-1043. doi: 10.1080/15592294.2015.11035781559-229410.1080/15592294.2015.110357826488939http://www.tandfonline.com/doi/full/10.1080/15592294.2015.1103578#.VpVLlTalw68info: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:RCAAP2023-07-21T12:42:52Zoai:repositorium.sdum.uminho.pt:1822/40589Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:40:12.501320Repositório 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 |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
title |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
spellingShingle |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication Luís, Ana Sílvia Pires epigenetic biomarkers histone covalent modifications histone methyltransferases NO66 Renal cell tumors SMYD2 SETD3 Ciências Médicas::Ciências da Saúde Science & Technology |
title_short |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
title_full |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
title_fullStr |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
title_full_unstemmed |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
title_sort |
Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication |
author |
Luís, Ana Sílvia Pires |
author_facet |
Luís, Ana Sílvia Pires Coimbra, Márcia Vieira Vieira, Filipa Quintela Pinheiro, Pedro Costa Santos, Rui Silva Dias, Paula C. Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline Saraiva Costa, Bruno Filipe Marques Henrique, Rui Jerónimo, Carmen |
author_role |
author |
author2 |
Coimbra, Márcia Vieira Vieira, Filipa Quintela Pinheiro, Pedro Costa Santos, Rui Silva Dias, Paula C. Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline Saraiva Costa, Bruno Filipe Marques Henrique, Rui Jerónimo, Carmen |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Luís, Ana Sílvia Pires Coimbra, Márcia Vieira Vieira, Filipa Quintela Pinheiro, Pedro Costa Santos, Rui Silva Dias, Paula C. Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline Saraiva Costa, Bruno Filipe Marques Henrique, Rui Jerónimo, Carmen |
dc.subject.por.fl_str_mv |
epigenetic biomarkers histone covalent modifications histone methyltransferases NO66 Renal cell tumors SMYD2 SETD3 Ciências Médicas::Ciências da Saúde Science & Technology |
topic |
epigenetic biomarkers histone covalent modifications histone methyltransferases NO66 Renal cell tumors SMYD2 SETD3 Ciências Médicas::Ciências da Saúde Science & Technology |
description |
Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
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/1822/40589 |
url |
http://hdl.handle.net/1822/40589 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pires-Luis, A. S., Vieira-Coimbra, M., Vieira, F. Q., Costa-Pinheiro, P., Silva-Santos, R., Dias, P. C., . . . Jeronimo, C. (2015). Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication. Epigenetics, 10(11), 1033-1043. doi: 10.1080/15592294.2015.1103578 1559-2294 10.1080/15592294.2015.1103578 26488939 http://www.tandfonline.com/doi/full/10.1080/15592294.2015.1103578#.VpVLlTalw68 |
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 |
Taylor and Francis |
publisher.none.fl_str_mv |
Taylor and Francis |
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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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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