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FN14 and GRP94 expression are prognostic predictive biomarkers_Oncotarget_2015.pdf (6.5 MB)

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2015-10-19

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cc-by (c) Martínez-Aranda et al., 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/69346

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

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Recurs relacionat

http://dx.doi.org/10.18632/oncotarget.5471

Resum

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.

Matèries

Marcadors bioquímics, Càncer de mama, Melanoma, Metàstasi

Matèries (anglès)

Biochemical markers, Breast cancer, Melanoma, Metastasis

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

MARTÍNEZ ARANDA, Antonio, HERNÁNDEZ, Vanessa, GUNEY, Emre, MUIXÍ, Laia, FOJ, Ruben, BAIXERAS, Núria, CUADRAS, Daniel, MORENO AGUADO, Víctor, URRUTICOECHEA RIBATE, Ander, GIL, Miguel, OLIVA MIGUEL, Baldomero, MORENO, Ferran, GONZÁLEZ SUÁREZ, Eva, VIDAL, Noemí, ANDREU, Xavier, SEGUÍ, Miquel a., BALLESTER, Rosa, CASTELLA, Eva, SIERRA JIMÉNEZ, Àngels. FN14 and GRP94 expression are prognostic/predictive biomarkers of   brain metastasis outcome that open up new therapeutic strategies. _Oncotarget_. 2015. Vol. 6, núm. 42, pàgs. 44255-44273. [consulta: 9 de febrer de 2026]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/69346]

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