Sequeiros, TamaraRigau, MarinaChiva, CristinaMontes, MelaniaGarcia-Grau, IolandaGarcia, MartaDiaz, SherleyCelma, AnaBijnsdorp, IreneCampos, AlexMauro, Primiano DiBorrós, SalvadorReventós Puigjaner, JaumeDoll, AndreasPaciucci Barzanti, RosannaPegtel, D. MichielTorres, Inés deSabidó Aguadé, EduardMorote, JuanOlivan Riera, Mireia2020-07-062020-07-062017-01-171949-2553https://hdl.handle.net/2445/167785Rapid and reliable diagnosis of prostate cancer (PCa) is highly desirable as current used methods lack specificity. In addition, identification of PCa biomarkers that can classify patients into high- and low-risk groups for disease progression at early stage will improve treatment decision-making. Here, we describe a set of protein-combination panels in urinary extracellular vesicles (EVs), defined by targeted proteomics and immunoblotting techniques that improve early non-invasive detection and stratification of PCa patients.We report a two-protein combination in urinary EVs that classifies benign and PCa patients (ADSV-TGM4), and a combination of five proteins able to significantly distinguish between high- and low-grade PCa patients (CD63-GLPK5-SPHM-PSA-PAPP). Proteins composing the panels were validated by immunohistochemistry assays in tissue microarrays (TMAs) confirming a strong link between the urinary EVs proteome and alterations in PCa tissues. Moreover, ADSV and TGM4 abundance yielded a high diagnostic potential in tissue and promising TGM4 prognostic power. These results suggest that the proteins identified in urinary EVs distinguishing high- and low grade PCa are a reflection of histological changes that may be a consequence of their functional involvement in PCa development. In conclusion, our study resulted in the identification of protein-combination panels present in urinary EVs that exhibit high sensitivity and specificity for PCa detection and patient stratification. Moreover, our study highlights the potential of targeted proteomic approaches-such as selected reaction monitoring (SRM)-as diagnostic assay for liquid biopsies via urinary EVs to improve diagnosis and prognosis of suspected PCa patients.17 p.application/pdfengcc-by (c) Sequeiros, Tamara et al., 2017http://creativecommons.org/licenses/by/3.0/esIndicadors biològicsOrinaCàncer de pròstataIndicators (Biology)UrineProstate cancerinfo:eu-repo/semantics/article6977512020-07-06info:eu-repo/semantics/openAccess27903962