Micro-RNA And mRNA Integrative Analysis Uncover Potential Diagnostic And Prognostic Markers In Penile Carcinomas

Hellen KUASNE, AC Camargo Cancer Center, Brazil
BARROS-FILHO M. 1 , BUSSO-LOPES A. 1 , PINHERO M. 1,2 , MUÑOZ J. 1 , SCAPULATEMPO-NETO C. 3 , FARIA E. 4 , GURIMARÃES G. 5 , ADEMAR L. 5 , AGOSTINHO A. 2 , TRINDADE-FILHO J. 2 , MARCHI F. 1 , DRIGO S. 2 , ROGATTO S. 1,2

1 1 CIPE - A. C. Camargo Cancer Center, São Paulo, Brazil
2 2 Department of Urology, Faculty of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
3 3 Department of Pathology, Barretos Cancer Hospital, São Paulo, Brazil.
4 4 Department of Urology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
5 5 Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil.

Purpose. Integrative analysis of transcriptomic and epigenetic profiles is a powerful method to identify molecular drivers of cancer development and progression. Aiming to contribute with the identification of molecular drivers, we investigated penile carcinomas (PeCa), a rare disease associated with high mortality and morbidity rate.
Patients and Methods. miRNA expression was performed using the TaqMan Human MicroRNA Array v2.0 (Applied Biosystems) in 23 PeCa tissues and 12 non-neoplastic penile tissue (NPT). Previously reported transcriptome expression results (Kuasne et al. Clin Epigenetics. 2015 Apr 18;7:46) were integrated with miRNA data.
Results. Eighty-one miRNA and 2,697 mRNAs differentially expressed were identified comparing tumor and non-neoplastic tissues. Integrative analysis revealed that 255 mRNAs were specifically regulated by 68 miRNAs in PeCa. For data confirmation, 8 miRNAs and 8 mRNAs were evaluated by RT-qPCR in an array-independent set of cases (PeCa=36; NPT=27) confirming the results. Molecular diagnostic classifiers with MMP1, MMP12 and PPARG transcripts were able to distinguish tumors from NPT with 92% of sensitivity and 83% of specificity. Similarly, three miRNAs (hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p) were able to discriminate tumors from NPT (82% of sensitivity and 74% of specificity). Higher MMP1 expression levels were able to predict lymph node metastasis more efficiently than clinical-pathological data.
Conclusion. To our knowledge, this is the first integrative analysis of miRNA and mRNA expression data in PeCa. The findings revealed molecular markers involved in the development of PeCa. Furthermore, MMP1 overexpression was as predictive marker of lymph node involvement and could be useful in the clinical practice.
Financial support: FAPESP and CNPq.