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FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies

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dc.contributor.author Martínez Aranda, Antonio
dc.contributor.author Hernández, Vanessa
dc.contributor.author Güney, Emre, 1983-
dc.contributor.author Muixí, Laia
dc.contributor.author Foj, Ruben
dc.contributor.author Baixeras, Núria
dc.contributor.author Cuadras, Daniel
dc.contributor.author Moreno, Víctor
dc.contributor.author Urruticoechea, Ander
dc.contributor.author Gil, Miguel
dc.contributor.author Oliva Miguel, Baldomero
dc.contributor.author Moreno, Ferran
dc.contributor.author González Suárez, Eva
dc.contributor.author Vidal, Noemí
dc.contributor.author Andreu, Xavier
dc.contributor.author Seguí, Miquel A.
dc.contributor.author Ballester, Rosa
dc.contributor.author Castella, Eva
dc.contributor.author Sierra, Angels
dc.date.accessioned 2016-02-11T15:59:10Z
dc.date.available 2016-02-11T15:59:10Z
dc.date.issued 2015
dc.identifier.citation Martínez-Aranda A, Hernández V, Guney E, Muixí L, Foj R, Baixeras N et al. FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies. Oncotarget. 2015;6(42):44254-73. DOI: 10.18632/oncotarget.5471
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/25793
dc.description.abstract Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.
dc.description.sponsorship This study was supported by grants from the Spanish Ministry of Health and Consumer Affairs FIS-PI10/00057 and FIS-PI14/00336, both from the I+D+I National Plan with the financial support from ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), and by grants from MIIN FIS2008–00114 and BIO2014-57518-R, 2014 SGR 530 and 2009-SGR-159 from the Generalitat de Catalunya, Fundació Privada Cellex Barcelona and the AECC (Spanish Association Against Cancer) Scientific Foundation
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Impact Journals
dc.relation.ispartof Oncotarget. 2015;6(42):44254-73
dc.rights © The Authors. This is the published version of an article http://dx.doi.org/10.18632/oncotarget.5471 that appeared in the journal Oncotarget. It is published under a Creative Commons Attribution 3.0 License
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.other Metàstasi
dc.subject.other Cervell
dc.title FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.5471
dc.subject.keyword Biomarkers
dc.subject.keyword Brain metastasis
dc.subject.keyword Breast cancer
dc.subject.keyword FN14
dc.subject.keyword GRP94
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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