Characterisation of the main PSA glycoforms in aggressive prostate cancer

Serum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosyl...

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Autores: Gratacós Mulleras, Anna, Duran Sidera, Adrià, Shehni, Akram Asadi, Ferrer-Batallé, Montserrat, Ramírez, Manel, Comet i Batlle, Josep, Llorens Duran, Rafael de, Saldova, Radka, Llop Escorihuela, Esther, Peracaula Miró, Rosa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/19068
Acceso en línea:http://hdl.handle.net/10256/19068
Access Level:acceso abierto
Palabra clave:Pròstata -- Càncer
Prostate -- Cancer
Marcadors bioquímics
Biochemical markers
Glicosilació
Glycosylation
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spelling Characterisation of the main PSA glycoforms in aggressive prostate cancerGratacós Mulleras, AnnaDuran Sidera, AdriàShehni, Akram AsadiFerrer-Batallé, MontserratRamírez, ManelComet i Batlle, JosepLlorens Duran, Rafael deSaldova, RadkaLlop Escorihuela, EstherPeracaula Miró, RosaPròstata -- CàncerProstate -- CancerMarcadors bioquímicsBiochemical markersGlicosilacióGlycosylationSerum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosylation is involved in neoplastic progression and specific changes in PSA glycosylation pattern, as the reduction in the percentage of α2,6-sialic acid (SA) are associated with PCa aggressiveness. In this study, we have characterised the main sialylated PSA glycoforms from blood serum of aggressive PCa patients and have compared with those of standard PSA from healthy individuals' seminal plasma. PSA was immunoprecipitated and α2,6-SA were separated from α2,3-SA glycoforms using SNA affinity chromatography. PSA N-glycans were released, labelled and analysed by hydrophilic interaction liquid chromatography combined with exoglycosidase digestions. The results showed that blood serum PSA sialylated glycoforms containing GalNAc residues were largely increased in aggressive PCa patients, whereas the disialylated core fucosylated biantennary structures with α2,6-SA, which are the major PSA glycoforms in standard PSA from healthy individuals, were markedly reduced in aggressive PCa. The identification of these main PSA glycoforms altered in aggressive PCa opens the way to design specific strategies to target them, which will be useful to improve PCa risk stratificationThis work was supported by Spanish Ministry of Science and Innovation (Grant BIO 2015-66356-R), the University of Girona (Grant MPCUdG2016/028), by the AGAUR-Generalitat of Catalunya (Grant 2014SGR0229), by Fundació La Marató de TV3 (201922-30-31) and by Roche Diagnostics (Barcelona, Spain; Grant IDI-20170423). A. Gratacos-Mulleras acknowledges funding support from the University of Girona for a pre-doctoral fellowship FI and A. Duran from Spanish Ministry of Science and Innovation for a FPU pre-doctoral fellowship and a mobility grant. Radka Saldova acknowledges funding from the Science foundation Ireland Starting Investigator Research grant (SFI SIRG) under grant number 13/SIRG/2164Nature Publishing GroupMinisterio de Economía y Competitividad (Espanya)2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/19068http://hdl.handle.net/10256/19068Scientific Reports, 2020, vol. 10, art. núm. 18974Articles publicats (D-B)Gratacós Mulleras, Anna Duran Sidera, Adrià Shehni, Akram Asadi Ferrer-Batallé, Montserrat Ramírez, Manel Comet i Batlle, Josep Llorens Duran, Rafael de Saldova, Radka Llop Escorihuela, Esther Peracaula Miró, Rosa 2020 Characterisation of the main PSA glycoforms in aggressive prostate cancer Scientific Reports 10 art. núm. 18974reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-75526-3info:eu-repo/semantics/altIdentifier/issn/2045-2322info:eu-repo/grantAgreement/MINECO//BIO2015-66356-RReconeixement 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10256/190682026-05-29T05:05:01Z
dc.title.none.fl_str_mv Characterisation of the main PSA glycoforms in aggressive prostate cancer
title Characterisation of the main PSA glycoforms in aggressive prostate cancer
spellingShingle Characterisation of the main PSA glycoforms in aggressive prostate cancer
Gratacós Mulleras, Anna
Pròstata -- Càncer
Prostate -- Cancer
Marcadors bioquímics
Biochemical markers
Glicosilació
Glycosylation
title_short Characterisation of the main PSA glycoforms in aggressive prostate cancer
title_full Characterisation of the main PSA glycoforms in aggressive prostate cancer
title_fullStr Characterisation of the main PSA glycoforms in aggressive prostate cancer
title_full_unstemmed Characterisation of the main PSA glycoforms in aggressive prostate cancer
title_sort Characterisation of the main PSA glycoforms in aggressive prostate cancer
dc.creator.none.fl_str_mv Gratacós Mulleras, Anna
Duran Sidera, Adrià
Shehni, Akram Asadi
Ferrer-Batallé, Montserrat
Ramírez, Manel
Comet i Batlle, Josep
Llorens Duran, Rafael de
Saldova, Radka
Llop Escorihuela, Esther
Peracaula Miró, Rosa
author Gratacós Mulleras, Anna
author_facet Gratacós Mulleras, Anna
Duran Sidera, Adrià
Shehni, Akram Asadi
Ferrer-Batallé, Montserrat
Ramírez, Manel
Comet i Batlle, Josep
Llorens Duran, Rafael de
Saldova, Radka
Llop Escorihuela, Esther
Peracaula Miró, Rosa
author_role author
author2 Duran Sidera, Adrià
Shehni, Akram Asadi
Ferrer-Batallé, Montserrat
Ramírez, Manel
Comet i Batlle, Josep
Llorens Duran, Rafael de
Saldova, Radka
Llop Escorihuela, Esther
Peracaula Miró, Rosa
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (Espanya)
dc.subject.none.fl_str_mv Pròstata -- Càncer
Prostate -- Cancer
Marcadors bioquímics
Biochemical markers
Glicosilació
Glycosylation
topic Pròstata -- Càncer
Prostate -- Cancer
Marcadors bioquímics
Biochemical markers
Glicosilació
Glycosylation
description Serum levels of prostate specific antigen (PSA) are commonly used for prostate cancer (PCa) detection. However, their lack of specificity to distinguish benign prostate pathologies from PCa, or indolent from aggressive PCa have prompted the study of new non-invasive PCa biomarkers. Aberrant glycosylation is involved in neoplastic progression and specific changes in PSA glycosylation pattern, as the reduction in the percentage of α2,6-sialic acid (SA) are associated with PCa aggressiveness. In this study, we have characterised the main sialylated PSA glycoforms from blood serum of aggressive PCa patients and have compared with those of standard PSA from healthy individuals' seminal plasma. PSA was immunoprecipitated and α2,6-SA were separated from α2,3-SA glycoforms using SNA affinity chromatography. PSA N-glycans were released, labelled and analysed by hydrophilic interaction liquid chromatography combined with exoglycosidase digestions. The results showed that blood serum PSA sialylated glycoforms containing GalNAc residues were largely increased in aggressive PCa patients, whereas the disialylated core fucosylated biantennary structures with α2,6-SA, which are the major PSA glycoforms in standard PSA from healthy individuals, were markedly reduced in aggressive PCa. The identification of these main PSA glycoforms altered in aggressive PCa opens the way to design specific strategies to target them, which will be useful to improve PCa risk stratification
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/19068
http://hdl.handle.net/10256/19068
url http://hdl.handle.net/10256/19068
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-75526-3
info:eu-repo/semantics/altIdentifier/issn/2045-2322
info:eu-repo/grantAgreement/MINECO//BIO2015-66356-R
dc.rights.none.fl_str_mv Reconeixement 4.0 Internacional
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconeixement 4.0 Internacional
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Scientific Reports, 2020, vol. 10, art. núm. 18974
Articles publicats (D-B)
Gratacós Mulleras, Anna Duran Sidera, Adrià Shehni, Akram Asadi Ferrer-Batallé, Montserrat Ramírez, Manel Comet i Batlle, Josep Llorens Duran, Rafael de Saldova, Radka Llop Escorihuela, Esther Peracaula Miró, Rosa 2020 Characterisation of the main PSA glycoforms in aggressive prostate cancer Scientific Reports 10 art. núm. 18974
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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