期刊
ONCOTARGET
卷 8, 期 3, 页码 4960-4976出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13634
关键词
prostate cancer; biomarkers; urine; extracellular vesicles; diagnosis
资金
- Instituto de Salud Carlos III (ISCIII) [PI11/02486, CD12/00475]
- Asociacion Espanola Contra el Cancer [AECC-JB-2013-02]
- IRSES, Belgium [PROTBIOFLUID - 269285]
- Vall d'Hebron Research Institute (VHIR)
- Instituto de Salud Carlos III - European Regional Development Fund(ERDF) [RD12/0036/0035]
- ISCIII [PT13/0001]
- Spanish Ministry of Economy and Competitiveness
- Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa [SEV-2012-0208]
- Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya [2014SGR678]
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.
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