Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

Fabio Albuquerque Marchi, David Correa Martins, Mateus Camargo Barros-Filho, Hellen Kuasne, Ariane Fidelis Busso Lopes, Helena Brentani, José Carlos de Souza Trindade Filho, Gustavo Cardoso Guimarães, Eliney Ferreira Faria, Cristovam Scapulatempo-Neto, Ademar Lopes, Silvia Regina Rogatto

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Resumé

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.

OriginalsprogEngelsk
Artikelnummer6707
TidsskriftScientific Reports
Vol/bind7
Udgave nummer1
Antal sider11
ISSN2045-2322
DOI
StatusUdgivet - 2017

Fingeraftryk

MicroRNAs
Penile Neoplasms
DNA Methylation
Immune System
Cell Cycle
Public Health
Messenger RNA
Neoplasms
Pyroptosis

Citer dette

Marchi, F. A., Martins, D. C., Barros-Filho, M. C., Kuasne, H., Busso Lopes, A. F., Brentani, H., ... Rogatto, S. R. (2017). Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma. Scientific Reports, 7(1), [6707]. https://doi.org/10.1038/s41598-017-06659-1
Marchi, Fabio Albuquerque ; Martins, David Correa ; Barros-Filho, Mateus Camargo ; Kuasne, Hellen ; Busso Lopes, Ariane Fidelis ; Brentani, Helena ; Trindade Filho, José Carlos de Souza ; Guimarães, Gustavo Cardoso ; Faria, Eliney Ferreira ; Scapulatempo-Neto, Cristovam ; Lopes, Ademar ; Rogatto, Silvia Regina. / Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma. I: Scientific Reports. 2017 ; Bind 7, Nr. 1.
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title = "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 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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Marchi, FA, Martins, DC, Barros-Filho, MC, Kuasne, H, Busso Lopes, AF, Brentani, H, Trindade Filho, JCDS, Guimarães, GC, Faria, EF, Scapulatempo-Neto, C, Lopes, A & Rogatto, SR 2017, 'Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma', Scientific Reports, bind 7, nr. 1, 6707. https://doi.org/10.1038/s41598-017-06659-1

Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma. / Marchi, Fabio Albuquerque; Martins, David Correa; Barros-Filho, Mateus Camargo; Kuasne, Hellen; Busso Lopes, Ariane Fidelis; Brentani, Helena; Trindade Filho, José Carlos de Souza; Guimarães, Gustavo Cardoso; Faria, Eliney Ferreira; Scapulatempo-Neto, Cristovam; Lopes, Ademar; Rogatto, Silvia Regina.

I: Scientific Reports, Bind 7, Nr. 1, 6707, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

AU - Marchi, Fabio Albuquerque

AU - Martins, David Correa

AU - Barros-Filho, Mateus Camargo

AU - Kuasne, Hellen

AU - Busso Lopes, Ariane Fidelis

AU - Brentani, Helena

AU - Trindade Filho, José Carlos de Souza

AU - Guimarães, Gustavo Cardoso

AU - Faria, Eliney Ferreira

AU - Scapulatempo-Neto, Cristovam

AU - Lopes, Ademar

AU - Rogatto, Silvia Regina

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41598-017-06659-1

DO - 10.1038/s41598-017-06659-1

M3 - Journal article

C2 - 28751665

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 6707

ER -