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, Antonioca
• dc.contributor.author Hernández, Vanessaca
• dc.contributor.author Güney, Emre, 1983-ca
• dc.contributor.author Muixí, Laiaca
• dc.contributor.author Foj, Rubenca
• dc.contributor.author Baixeras, Núriaca
• dc.contributor.author Cuadras, Danielca
• dc.contributor.author Moreno, Víctorca
• dc.contributor.author Urruticoechea, Anderca
• dc.contributor.author Gil, Miguelca
• dc.contributor.author Oliva Miguel, Baldomeroca
• dc.contributor.author Moreno, Ferranca
• dc.contributor.author González Suárez, Evaca
• dc.contributor.author Vidal, Noemíca
• dc.contributor.author Andreu, Xavierca
• dc.contributor.author Seguí, Miquel A.ca
• dc.contributor.author Ballester, Rosaca
• dc.contributor.author Castella, Evaca
• dc.contributor.author Sierra, Angelsca
• dc.date.accessioned 2016-02-11T15:59:10Z
• dc.date.available 2016-02-11T15:59:10Z
• dc.date.issued 2015
• 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.ca
• 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/pdfca
• 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.5471ca
• dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.5471
• dc.identifier.issn 1949-2553
• dc.identifier.uri http://hdl.handle.net/10230/25793
• dc.language.iso engca
• dc.publisher Impact Journalsca
• 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 Licenseca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/3.0/ca
• dc.subject.keyword Biomarkers
• dc.subject.keyword Brain metastasis
• dc.subject.keyword Breast cancer
• dc.subject.keyword FN14
• dc.subject.keyword GRP94
• dc.subject.other Metàstasica
• dc.subject.other Cervellca
• dc.title FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategiesca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca