Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer

// Felix Royo 1, 2, * , Patricia Zuñiga-Garcia 1, * , Verónica Torrano 1, * , Ana Loizaga 3, * , Pilar Sanchez-Mosquera 1 , Aitziber Ugalde-Olano 4 , Esperanza González 1 , Ana R. Cortazar 1 , Laura Palomo 1 , Sonia Fernández-Ruiz 1 , Isabel Lacasa-Viscasillas 3 , Maria Berdasco 5 , James D. Sutherland 1 , Rosa Barrio 1 , Amaia Zabala-Letona 1 , Natalia Martín-Martín 1 , Amaia Arruabarrena-Aristorena 1 , Lorea Valcarcel-Jimenez 1 , Alfredo Caro-Maldonado 1 , Jorge Gonzalez-Tampan 3 , Guido Cachi-Fuentes 3 , Manel Esteller 5 , Ana M. Aransay 1, 2 , Miguel Unda 3 , Juan M. Falcón-Pérez 1, 2, 6, Ω , Arkaitz Carracedo 1, 6, 7, Ω 1 CIC bioGUNE, Bizkaia Technology Park, Biscay, Spain 2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain 3 Department of Urology, Basurto University Hospital, Bilbao, Spain 4 Department of Pathology, Basurto University Hospital, Bilbao, Spain 5 Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain 6 Ikerbasque, Basque Foundation for Science, Bizkaia, Spain 7 Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bizkaia, Spain * These authors contributed equally to this work Ω These authors contributed equally to this work Correspondence to: Arkaitz Carracedo, e-mail: acarracedo@cicbiogune.es Juan M. Falcón-Pérez, e-mail: jfalcon@cicbiogune.es Keywords: extracellular vesicles, exosomes, prostate cancer, urine biomakers Received: August 18, 2015 Accepted: November 26, 2015 Published: January 12, 2016 ABSTRACT Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa.