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/10400.22/14164 |
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 3 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 [area under curve (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 prognosticationBiomarkers, TumorCarcinoma, Renal CellChromosomal Proteins, Non-HistoneDiagnosis, DifferentialEarly Detection of CancerGene Expression Regulation, NeoplasticHistone DemethylasesHistone-Lysine N-MethyltransferaseKidney NeoplasmsPrognosisUp-RegulationRenal 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 3 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 [area under curve (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.Taylor & FrancisRepositório Científico do Instituto Politécnico do PortoPires-Luís, Ana SílviaVieira-Coimbra, MarciaQuintela Vieira, Ana FilipaCosta-Pinheiro, PedroSilva-Santos, RuiDias, Paula CAntunes, LuísLobo, FranciscoOliveira, JorgeGonçalves, Céline SCosta, Bruno MHenrique, RuiJerónimo, Carmen2019-06-28T15:50:51Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/14164engPires-Luís, A. S., Vieira-Coimbra, M., Vieira, F. Q., Costa-Pinheiro, P., Silva-Santos, R., Dias, P. C., Antunes, L., Lobo, F., Oliveira, J., Gonçalves, C. S., Costa, B. M., Henrique, R., & Jerónimo, C. (2015). Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication. Epigenetics, 10(11), 1033–1043. https://doi.org/10.1080/15592294.2015.110357810.1080/15592294.2015.1103578info: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:RCAAP2023-12-20T01:53:29Zoai:recipp.ipp.pt:10400.22/14164Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:33:59.092693Repositório 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 Pires-Luís, Ana Sílvia Biomarkers, Tumor Carcinoma, Renal Cell Chromosomal Proteins, Non-Histone Diagnosis, Differential Early Detection of Cancer Gene Expression Regulation, Neoplastic Histone Demethylases Histone-Lysine N-Methyltransferase Kidney Neoplasms Prognosis Up-Regulation |
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 |
Pires-Luís, Ana Sílvia |
author_facet |
Pires-Luís, Ana Sílvia Vieira-Coimbra, Marcia Quintela Vieira, Ana Filipa Costa-Pinheiro, Pedro Silva-Santos, Rui Dias, Paula C Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline S Costa, Bruno M Henrique, Rui Jerónimo, Carmen |
author_role |
author |
author2 |
Vieira-Coimbra, Marcia Quintela Vieira, Ana Filipa Costa-Pinheiro, Pedro Silva-Santos, Rui Dias, Paula C Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline S Costa, Bruno M Henrique, Rui Jerónimo, Carmen |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Pires-Luís, Ana Sílvia Vieira-Coimbra, Marcia Quintela Vieira, Ana Filipa Costa-Pinheiro, Pedro Silva-Santos, Rui Dias, Paula C Antunes, Luís Lobo, Francisco Oliveira, Jorge Gonçalves, Céline S Costa, Bruno M Henrique, Rui Jerónimo, Carmen |
dc.subject.por.fl_str_mv |
Biomarkers, Tumor Carcinoma, Renal Cell Chromosomal Proteins, Non-Histone Diagnosis, Differential Early Detection of Cancer Gene Expression Regulation, Neoplastic Histone Demethylases Histone-Lysine N-Methyltransferase Kidney Neoplasms Prognosis Up-Regulation |
topic |
Biomarkers, Tumor Carcinoma, Renal Cell Chromosomal Proteins, Non-Histone Diagnosis, Differential Early Detection of Cancer Gene Expression Regulation, Neoplastic Histone Demethylases Histone-Lysine N-Methyltransferase Kidney Neoplasms Prognosis Up-Regulation |
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 3 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 [area under curve (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 2019-06-28T15:50:51Z |
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/10400.22/14164 |
url |
http://hdl.handle.net/10400.22/14164 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pires-Luís, A. S., Vieira-Coimbra, M., Vieira, F. Q., Costa-Pinheiro, P., Silva-Santos, R., Dias, P. C., Antunes, L., Lobo, F., Oliveira, J., Gonçalves, C. S., Costa, B. M., Henrique, R., & Jerónimo, C. (2015). Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication. Epigenetics, 10(11), 1033–1043. https://doi.org/10.1080/15592294.2015.1103578 10.1080/15592294.2015.1103578 |
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 & Francis |
publisher.none.fl_str_mv |
Taylor & Francis |
dc.source.none.fl_str_mv |
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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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