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Pàgina inicial > Articles > Articles publicats > Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer |
Data: | 2016 |
Resum: | 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. |
Ajuts: | Instituto de Salud Carlos III PI11-02486 Instituto de Salud Carlos III CD12-00475 Instituto de Salud Carlos III RD12-0036-0035 Instituto de Salud Carlos III PT13-0001 Ministerio de Economía y Competitividad SEV-2012-0208 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR678 |
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). |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Prostate cancer ; Biomarkers ; Urine ; Extracellular vesicles ; Diagnosis |
Publicat a: | Oncotarget, Vol. 8 (november 2016) , p. 4960-4976, ISSN 1949-2553 |
17 p, 5.0 MB |