Journal
ONCOTARGET
Volume 8, Issue 3, Pages 4960-4976Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13634
Keywords
prostate cancer; biomarkers; urine; extracellular vesicles; diagnosis
Categories
Funding
- 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]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available