Author(s): 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]
Date: 2018
Persistent ID: http://hdl.handle.net/11449/174966
Origin: Oasisbr
Made available in DSpace on 2018-12-11T17:13:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01
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.
A.C.Camargo Cancer Center
Center of Mathematics Computing and Cognition Federal University of ABC UFABC
Brazilian Biosciences National Laboratory (LNBio)
Department of Psychiatry Medical School University of Sao Paulo-USP
Department of Urology Faculty of Medicine Sao Paulo State University-UNESP
Department of Urology Barretos Cancer Hospital
Molecular Oncology Research Center Barretos Cancer Hospital
Department of Clinical Genetics Vejle Hospital Institute of Regional Health University of Southern Denmark
Department of Urology Faculty of Medicine Sao Paulo State University-UNESP
