Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.
Cancers. 2021 Sep 23*** epublish ***
Tatiane Katsue Furuya, Claudio Bovolenta Murta, Alexis Germán Murillo Carrasco, Miyuki Uno, Laura Sichero, Luisa Lina Villa, Leonardo Cardilli, Rafael Ferreira Coelho, Giuliano Betoni Guglielmetti, Mauricio Dener Cordeiro, Katia Ramos Moreira Leite, William Carlos Nahas, Roger Chammas, José Pontes
Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo CEP 01246-000, SP, Brazil., Departamento de Urologia, ICESP, HCFMUSP, Sao Paulo CEP 01246-000, SP, Brazil., Departamento de Patologia, ICESP, HCFMUSP, Sao Paulo CEP 01246-000, SP, Brazil.