Abstract 5399: Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis
Authors: Furuya Tatiane K. , Murta Claudio B. , Jr José Pontes , Uno Miyuki , Carrasco Alexis , Sichero Laura C. , Villa Luisa L. , Coelho Rafael F. , Guglielmetti Giuliano B. , Cordeiro Mauricio D. , Leite Kátia R. , Srougi Miguel , Chammas Roger , Nahas William C. 
Published: August 2018

Abstract
Introduction and objective: Penile cancer is a rare disease that has high morbidity and mortality rates. While a few biomarkers related to prognosis have been previously described to date none of them was adopted in clinical practice. Our aim was to identify a molecular signature based on miRNA expression levels that could identify those patients with high risk of metastatic penile carcinoma.
Methods: We prospectively collected fresh samples of primary tumors from 11 patients with squamous cell penile carcinoma who underwent surgical treatment between July/2015 and June/2017. Five patients had localized disease (non-metastatic group) and 6 had inguinal lymph node metastases (metastatic group). RNA was purified and microarray analysis was performed using miRNA 4.0 Genechip (Affymetrix). We identified differentially expressed miRNAs (DEmiRs) comparing metastatic in relation to non-metastatic groups using TAC Software (Affymetrix), fold change (FC) &gt; 1.5 and p&lt;0.05. Their validated/predicted targets were investigated using miRTarBase 7.0, mirWalk 2.0 and/or MetaCore 6.32 softwares. Enrichment Pathways analysis was performed using Enrichr. Up/downstream interaction networks were identified by MetaCore v6.32 software.
Results: Twenty two DEmiRs (17 up- and 5 downregulated) were identified when comparing metastatic in relation to non-metastatic patients. Hierarchical clustering analysis showed a set of 7 DEmiRs (miR-181c-5p, 744-5p, 196b-5p, 200a-5p, 152-3p, 421, 149-5p) which clustered samples according to prognosis. Network interaction analyses identified transcriptional factors (NANOG, Oct-3/4, SOX2 and c-Jun) that commonly regulate those DEmiRs. Moreover, TGFB, CMYC, RICTOR, ADAM-17 and PTEN are some of the common targets of those DEmiRs and are more likely to be deregulated. Validated and predicted targets of these 7 DEmiRs were found enriched in relevant pathways such as “Proteoglycans in cancer”, “Pathways in cancer”, “miRNAs in cancer” and “Signaling pathways regulating pluripotency of stem cells”. Among their targets, CMYC, SP1, ESR1 and AR are examples of hubs which presented the highest number of network interactions.
Conclusions: We found 7 DEmiRs correlated with prognosis and capable of discriminating metastatic from non-metastatic tumors. In addition, their targets are enriched in cancer-related pathways and could be potential biomarkers for prognosis in penile cancer.
Citation Format: Tatiane K. Furuya, Claudio B. Murta, José Pontes Jr, Miyuki Uno, Alexis Carrasco, Laura C. Sichero, Luisa L. Villa, Rafael F. Coelho, Giuliano B. Guglielmetti, Mauricio D. Cordeiro, Kátia R. Leite, Miguel Srougi, Roger Chammas, William C. Nahas. Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5399.