Web of Science: 35 citas, Scopus: 36 citas, Google Scholar: citas,
Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer
Sequeiros, Tamara (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rigau, Marina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Chiva, Cristina (Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain)
Montes, Melania (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Grau, Iolanda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Diaz, Sherley (Hospital Universitari Vall d'Hebron)
Celma, Ana (Hospital Universitari Vall d'Hebron)
Bijnsdorp, Irene (Department of Urology, VU University Medical Center, Amsterdam, The Netherlands)
Campos, Alex (Sanford-Burnham Medical Research Institute, La Jolla, California, USA)
Di Mauro, Primiano (Sagetis-Biotech; Grup d'Enginyeria de Materials (GEMAT) Institut Químic de Sarrià, Barcelona, Spain)
Borrós, Salvador (Sagetis-Biotech; Grup d'Enginyeria de Materials (GEMAT) Institut Químic de Sarrià, Barcelona, Spain)
Reventós, Jaume (IDIBELL-Bellvitge Biomedical Research Institute, Barcelona, Spain)
Doll, Andreas (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Paciucci, Rosanna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pegtel, Michiel (Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands)
de Torres, Inés (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sabidó, Eduard (Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain)
Morote Robles, Juan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Olivan, Mireia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha: 2016
Resumen: 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.
Nota: Altres ajuts: The study was supported by grants AECC-JB-2013-02 of Asociación Española Contra el Cáncer, 7th Framework Programe, IRSES (PROTBIOFLUID −269285) - Belgium, pre-doctoral fellowship of Vall d'Hebron Research Institute (VHIR) and cofinanced by the European Regional Development Fund(ERDF).
Nota: Número d'acord de subvenció ISCIII/PI11-02486
Nota: Número d'acord de subvenció ISCIII/CD12-00475
Nota: Número d'acord de subvenció ISCIII/RD12-0036-0035
Nota: Número d'acord de subvenció ISCIII/PT13-0001
Nota: Número d'acord de subvenció MINECO/SEV-2012-0208
Nota: Número d'acord de subvenció AGAUR/2014SGR678
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès
Documento: article ; recerca ; publishedVersion
Materia: Prostate cancer ; Biomarkers ; Urine ; Extracellular vesicles ; Diagnosis
Publicado en: Oncotarget, Vol. 8 (november 2016) , p. 4960-4976, ISSN 1949-2553

DOI: 10.18632/oncotarget.13634
PMID: 27903962


17 p, 5.0 MB

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