Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer

Sequeiros, Tamara; Rigau, Marina; Chiva, Cristina; Montes, Melania; Garcia-Grau, Iolanda; Garcia, Marta; Diaz, Sherley; Celma, Anna; Bijnsdorp, Irene; Campos, Alex; Di Mauro, Primiano; Borrós, Salvador; Reventós, Jaume; Doll, Andreas; Paciucci, Rosanna; Pegtel, Michiel; Torres, Inés de; Sabidó Aguadé, Eduard, 1981-; Morote, Juan; Olivan, Mireia

Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer

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dc.contributor.author Sequeiros, Tamara
dc.contributor.author Rigau, Marina
dc.contributor.author Chiva, Cristina
dc.contributor.author Montes, Melania
dc.contributor.author Garcia-Grau, Iolanda
dc.contributor.author Garcia, Marta
dc.contributor.author Diaz, Sherley
dc.contributor.author Celma, Anna
dc.contributor.author Bijnsdorp, Irene
dc.contributor.author Campos, Alex
dc.contributor.author Di Mauro, Primiano
dc.contributor.author Borrós, Salvador
dc.contributor.author Reventós, Jaume
dc.contributor.author Doll, Andreas
dc.contributor.author Paciucci, Rosanna
dc.contributor.author Pegtel, Michiel
dc.contributor.author Torres, Inés de
dc.contributor.author Sabidó Aguadé, Eduard, 1981-
dc.contributor.author Morote, Juan
dc.contributor.author Olivan, Mireia
dc.date.accessioned 2025-02-04T07:32:47Z
dc.date.available 2025-02-04T07:32:47Z
dc.date.issued 2017
dc.description.abstract 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.en
dc.description.sponsorship The study was supported by grants PI11/02486 and CD12/00475 of Instituto de Salud Carlos III (ISCIII), 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 by Instituto de Salud Carlos III, grant RD12/0036/0035 cofinanced by the European Regional Development Fund(ERDF). The CRG/UPF Proteomics Unit is part of the “Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)” supported by grant PT13/0001 of ISCIII and Spanish Ministry of Economy and Competitiveness. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208, and from “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2014SGR678).en
dc.format.mimetype application/pdf
dc.identifier.citation Sequeiros T, Rigau M, Chiva C, Montes M, Garcia-Grau I, Garcia M, et al. Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer. Oncotarget. 2017 Jan 17;8(3):4960-76. DOI: 10.18632/oncotarget.13634
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.13634
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/69471
dc.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartof Oncotarget. 2017 Jan 17;8(3):4960-76
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/269285
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV-2012-0208
dc.rights All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Prostate canceren
dc.subject.keyword Biomarkersen
dc.subject.keyword Urineen
dc.subject.keyword Extracellular vesiclesen
dc.subject.keyword Diagnosisen
dc.title Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate canceren
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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