Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer
Por:
Sequeiros T, Rigau M, Chiva C, Montes M, Garcia-Grau I, Garcia-López M, Diaz S, Celma A, Bijnsdorp I, Campos A, Di Mauro P, Borrós S, Reventós J, Doll A, Paciucci R, Pegtel M, de Torres I, Sabidó E, Morote J and Olivan M
Publicada:
17 ene 2017
Categoría:
Oncology
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.
Filiaciones:
Sequeiros T:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Rigau M:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Chiva C:
Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona, Spain
Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain
Montes M:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Garcia-Grau I:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Garcia-López M:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Diaz S:
Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
Celma A:
Department of Urology, Vall d'Hebron University Hospital, Barcelona, Spain
Bijnsdorp I:
Department of Urology, VU University Medical Center, Amsterdam, The Netherlands
Campos A:
Sanford-Burnham Medical Research Institute, La Jolla, California, USA
Di Mauro P:
Sagetis-Biotech
Grup d'Enginyeria de Materials (GEMAT) Institut Químic de Sarrià, Barcelona, Spain
Borrós S:
Sagetis-Biotech
Grup d'Enginyeria de Materials (GEMAT) Institut Químic de Sarrià, Barcelona, Spain
Reventós J:
Departement of Basic Science, International University of Catalonia, Barcelona, Spain
IDIBELL-Bellvitge Biomedical Research Institute, Barcelona, Spain
Doll A:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Paciucci R:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Pegtel M:
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
de Torres I:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
Sabidó E:
Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona, Spain
Proteomics Unit, Universitat Pompeu Fabra, Barcelona, Spain
Morote J:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Department of Urology, Vall d'Hebron University Hospital, Barcelona, Spain
Olivan M:
Group of Biomedical Research in Urology, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
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