Rapid 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.
Oncotarget. 2016 Jan 26 [Epub ahead of print]
Tamara Sequeiros, Marina Rigau, Cristina Chiva, Melania Montes, Iolanda Garcia-Grau, Marta Garcia, Sherley Diaz, Ana Celma, Irene Bijnsdorp, Alex Campos, Primiano Di Mauro, Salvador Borrós, Jaume Reventós, Andreas Doll, Rosanna Paciucci, Michiel Pegtel, Inés de Torres, Eduard Sabidó, Juan Morote, Mireia Olivan
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain., Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona, Spain., Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain., Department of Urology, Vall d'Hebron University Hospital, Barcelona, Spain., Department of Urology, VU University Medical Center, Amsterdam, The Netherlands., Sanford-Burnham Medical Research Institute, La Jolla, California, USA., Sagetis-Biotech; Grup d'Enginyeria de Materials (GEMAT) Institut Químic de Sarrià, Barcelona, Spain., Departement of Basic Science, International University of Catalonia, Barcelona, Spain., Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.