Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

Abstract 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 expres...

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Autores principales:	Fabio Albuquerque Marchi, David Correa Martins, Mateus Camargo Barros-Filho, Hellen Kuasne, Ariane Fidelis Busso Lopes, Helena Brentani, Jose Carlos Souza Trindade Filho, Gustavo Cardoso Guimarães, Eliney F. Faria, Cristovam Scapulatempo-Neto, Ademar Lopes, Silvia Regina Rogatto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/567d21a2e38742ad89f2318f9882dae3
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spelling	oai:doaj.org-article:567d21a2e38742ad89f2318f9882dae32021-12-02T11:41:19ZMultidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma10.1038/s41598-017-06659-12045-2322https://doaj.org/article/567d21a2e38742ad89f2318f9882dae32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06659-1https://doaj.org/toc/2045-2322Abstract 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.Fabio Albuquerque MarchiDavid Correa MartinsMateus Camargo Barros-FilhoHellen KuasneAriane Fidelis Busso LopesHelena BrentaniJose Carlos Souza Trindade FilhoGustavo Cardoso GuimarãesEliney F. FariaCristovam Scapulatempo-NetoAdemar LopesSilvia Regina RogattoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabio Albuquerque Marchi David Correa Martins Mateus Camargo Barros-Filho Hellen Kuasne Ariane Fidelis Busso Lopes Helena Brentani Jose Carlos Souza Trindade Filho Gustavo Cardoso Guimarães Eliney F. Faria Cristovam Scapulatempo-Neto Ademar Lopes Silvia Regina Rogatto Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma
description	Abstract 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.
format	article
author	Fabio Albuquerque Marchi David Correa Martins Mateus Camargo Barros-Filho Hellen Kuasne Ariane Fidelis Busso Lopes Helena Brentani Jose Carlos Souza Trindade Filho Gustavo Cardoso Guimarães Eliney F. Faria Cristovam Scapulatempo-Neto Ademar Lopes Silvia Regina Rogatto
author_facet	Fabio Albuquerque Marchi David Correa Martins Mateus Camargo Barros-Filho Hellen Kuasne Ariane Fidelis Busso Lopes Helena Brentani Jose Carlos Souza Trindade Filho Gustavo Cardoso Guimarães Eliney F. Faria Cristovam Scapulatempo-Neto Ademar Lopes Silvia Regina Rogatto
author_sort	Fabio Albuquerque Marchi
title	Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma
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
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/567d21a2e38742ad89f2318f9882dae3
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Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

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