Título:
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Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer
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Autor/a:
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Sequeiros, Tamara; Rigau, Marina; Chiva, Cristina; Montes, Melania; Garcia-Grau, Iolanda; García, Marta; Diaz, Sherley; Celma, Ana; Bijnsdorp, Irene; Campos, Alex; Di Mauro, Primiano; Borrós, Salvador; Reventós, Jaume; Doll, Andreas; Paciucci, Rosanna; Pegtel, Michiel; de Torres, Inés; Sabidó, Eduard; Morote Robles, Juan; Olivan, M.; Universitat Autònoma de Barcelona
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Abstract:
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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). |
Abstract:
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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. |
Materia(s):
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-Prostate cancer -Biomarkers -Urine -Extracellular vesicles -Diagnosis |
Derechos:
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open access
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Article |
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Uri:
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https://ddd.uab.cat/record/186043
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