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Página principal > Artículos > Artículos publicados > FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
Fecha: | 2015 |
Resumen: | 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. |
Ayudas: | Instituto de Salud Carlos III FIS-PI10/00057 Instituto de Salud Carlos III FIS-PI14/00336 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-530 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009-SGR-159 |
Nota: | Altres ajuts: 2014 SGR 530 i 2009-SGR-159 de la Generalitat de Catalunya, Fundació Privada Cellex Barcelona i de l'Asociación Española Contra el Cáncer |
Nota: | Altres ajuts: MIIN/FIS2008-00114 |
Nota: | Altres ajuts: MIIN/BIO2014-57518-R |
Derechos: | Tots els drets reservats. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Marcadors bioquímics ; FN14 ; GRP94 ; Biomarkers ; Brain metastasis ; Breast cancer |
Publicado en: | Oncotarget, Vol. 6 Núm. 42 (December 2015) , ISSN 1949-2553 |
20 p, 6.5 MB |