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.

Details

Title
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma
Author
Fabio Albuquerque Marchi 1 ; David Correa Martins 2 ; Mateus Camargo Barros-Filho 1 ; Kuasne, Hellen 1 ; Ariane Fidelis Busso Lopes 3 ; Brentani, Helena 4 ; Jose Carlos Souza Trindade Filho 5 ; Gustavo Cardoso Guimarães 1 ; Faria, Eliney F 6 ; Scapulatempo-Neto, Cristovam 7 ; Lopes, Ademar 1 ; Rogatto, Silvia Regina 8 

 A.C.Camargo Cancer Center, São Paulo, SP, Brazil 
 Center of Mathematics, Computing and Cognition, Federal University of ABC – UFABC, Santo André, SP, Brazil 
 Brazilian Biosciences National Laboratory (LNBio), Campinas, SP, Brazil 
 Department of Psychiatry, Medical School, University of Sao Paulo – USP, São Paulo, SP, Brazil 
 Department of Urology, Faculty of Medicine, Sao Paulo State University - UNESP, Botucatu, SP, Brazil 
 Department of Urology, Barretos Cancer Hospital, São Paulo, Brazil 
 Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil 
 Department of Urology, Faculty of Medicine, Sao Paulo State University - UNESP, Botucatu, SP, Brazil; Department of Clinical Genetics, Vejle Hospital and Institute of Regional Health, University of Southern Denmark, Odense, Denmark 
Pages
1-11
Publication year
2017
Publication date
Jul 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1956171424
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.