Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

Detalhes bibliográficos
Autor(a) principal: Marchi, Fabio Albuquerque
Data de Publicação: 2017
Outros Autores: 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]
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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spelling 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)
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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)
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