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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

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Kuasne, Hellen ; Barros-Filho, Mateus C. ; Busso-Lopes, Ariane ; Marchi, Fabio A. ; Pinheiro, Maisa ; Munoz, Juan J. M. ; Scapulatempo-Neto, Cristovam ; Faria, Eliney F. ; Guimaraes, Gustavo C. ; Lopes, Ademar ; Trindade-Filho, Jose C. S. ; Domingues, Maria Aparecida C. ; Drigo, Sandra A. ; Rogatto, Silvia R.
Total Authors: 14
Document type: Journal article
Source: ONCOTARGET; v. 8, n. 9, p. 15294-15306, 2017.
Web of Science Citations: 12
Abstract

Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa. (AU)

FAPESP's process: 09/52088-3 - Cancer of the penis, a real Brazilian problem: from morphology to molecular etiopathogenesis
Grantee:José Vassallo
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/03667-6 - Functional study in penis carcimomas for the validation of candidate molecular markers obtained from integrated global analyzes (genomics, transcriptomics and DNA methylation)
Grantee:Hellen Kuasne
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 10/51601-6 - Profile methyla tion in penile carcinoma
Grantee:Silvia Regina Rogatto
Support type: Regular Research Grants