Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

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Marchi, Fabio Albuquerque ; Martins, David Correa ; Barros-Filho, Mateus Camargo ; Kuasne, Hellen ; Busso Lopes, Ariane Fidelis ; Brentani, Helena ; Souza Trindade Filho, Jose Carlos ; Guimaraes, Gustavo Cardoso ; Faria, Eliney F. ; Scapulatempo-Neto, Cristovam ; Lopes, Ademar ; Rogatto, Silvia Regina

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, JUL 27 2017.
• Web of Science Citations: 9

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 integrative methodology combining 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. (AU)

• FAPESP's process: 09/52088-3 - Cancer of the penis, a real Brazilian problem: from morphology to molecular etiopathogenesis
• Grantee: José Vassallo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/51601-6 - Profile methyla tion in penile carcinoma
• Grantee: Silvia Regina Rogatto
• Support Opportunities: Regular Research Grants