Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-017-06659-1 http://hdl.handle.net/11449/174966 |
Resumo: | Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer. |
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Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinomaMolecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer.A.C.Camargo Cancer CenterCenter of Mathematics Computing and Cognition Federal University of ABC UFABCBrazilian Biosciences National Laboratory (LNBio)Department of Psychiatry Medical School University of Sao Paulo-USPDepartment of Urology Faculty of Medicine Sao Paulo State University-UNESPDepartment of Urology Barretos Cancer HospitalMolecular Oncology Research Center Barretos Cancer HospitalDepartment of Clinical Genetics Vejle Hospital Institute of Regional Health University of Southern DenmarkDepartment of Urology Faculty of Medicine Sao Paulo State University-UNESPA.C.Camargo Cancer CenterUniversidade Federal do ABC (UFABC)Brazilian Biosciences National Laboratory (LNBio)Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Barretos Cancer HospitalUniversity of Southern DenmarkMarchi, Fabio AlbuquerqueMartins, David CorreaBarros-Filho, Mateus CamargoKuasne, HellenBusso Lopes, Ariane FidelisBrentani, HelenaTrindade Filho, Jose Carlos Souza [UNESP]Guimarães, Gustavo CardosoFaria, Eliney F.Scapulatempo-Neto, CristovamLopes, AdemarRogatto, Silvia Regina [UNESP]2018-12-11T17:13:40Z2018-12-11T17:13:40Z2017-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1038/s41598-017-06659-1Scientific Reports, v. 7, n. 1, 2017.2045-2322http://hdl.handle.net/11449/17496610.1038/s41598-017-06659-12-s2.0-850263539132-s2.0-85026353913.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reports1,533info:eu-repo/semantics/openAccess2024-09-03T14:29:57Zoai:repositorio.unesp.br:11449/174966Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T14:29:57Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
title |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
spellingShingle |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma Marchi, Fabio Albuquerque |
title_short |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
title_full |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
title_fullStr |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
title_full_unstemmed |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
title_sort |
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma |
author |
Marchi, Fabio Albuquerque |
author_facet |
Marchi, Fabio Albuquerque Martins, David Correa Barros-Filho, Mateus Camargo Kuasne, Hellen Busso Lopes, Ariane Fidelis Brentani, Helena Trindade Filho, Jose Carlos Souza [UNESP] Guimarães, Gustavo Cardoso Faria, Eliney F. Scapulatempo-Neto, Cristovam Lopes, Ademar Rogatto, Silvia Regina [UNESP] |
author_role |
author |
author2 |
Martins, David Correa Barros-Filho, Mateus Camargo Kuasne, Hellen Busso Lopes, Ariane Fidelis Brentani, Helena Trindade Filho, Jose Carlos Souza [UNESP] Guimarães, Gustavo Cardoso Faria, Eliney F. Scapulatempo-Neto, Cristovam Lopes, Ademar Rogatto, Silvia Regina [UNESP] |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
A.C.Camargo Cancer Center Universidade Federal do ABC (UFABC) Brazilian Biosciences National Laboratory (LNBio) Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Barretos Cancer Hospital University of Southern Denmark |
dc.contributor.author.fl_str_mv |
Marchi, Fabio Albuquerque Martins, David Correa Barros-Filho, Mateus Camargo Kuasne, Hellen Busso Lopes, Ariane Fidelis Brentani, Helena Trindade Filho, Jose Carlos Souza [UNESP] Guimarães, Gustavo Cardoso Faria, Eliney F. Scapulatempo-Neto, Cristovam Lopes, Ademar Rogatto, Silvia Regina [UNESP] |
description |
Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12-01 2018-12-11T17:13:40Z 2018-12-11T17:13:40Z |
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://dx.doi.org/10.1038/s41598-017-06659-1 Scientific Reports, v. 7, n. 1, 2017. 2045-2322 http://hdl.handle.net/11449/174966 10.1038/s41598-017-06659-1 2-s2.0-85026353913 2-s2.0-85026353913.pdf |
url |
http://dx.doi.org/10.1038/s41598-017-06659-1 http://hdl.handle.net/11449/174966 |
identifier_str_mv |
Scientific Reports, v. 7, n. 1, 2017. 2045-2322 10.1038/s41598-017-06659-1 2-s2.0-85026353913 2-s2.0-85026353913.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports 1,533 |
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.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
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1810021367383326720 |