FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies
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 includ...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2015 |
| Country: | España |
| Institution: | Universitat Pompeu Fabra |
| Repository: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/25793 |
| Online Access: | http://hdl.handle.net/10230/25793 http://dx.doi.org/10.18632/oncotarget.5471 |
| Access Level: | Open access |
| Keyword: | Metàstasi Cervell Biomarkers Brain metastasis Breast cancer FN14 GRP94 |
| _version_ | 1878742589197254656 |
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| author | Martínez Aranda, Antonio |
| author2 | Hernández, Vanessa Güney, Emre, 1983- Muixí, Laia Foj, Ruben Baixeras, Núria Cuadras, Daniel Moreno, Víctor Urruticoechea, Ander Gil, Miguel Oliva Miguel, Baldomero Moreno, Ferran González Suárez, Eva Vidal, Noemí Andreu, Xavier Seguí, Miquel A. Ballester, Rosa Castella, Eva Sierra, Angels |
| author2_role | author author author author author author author author author author author author author author author author author author |
| author_browse | Andreu, Xavier Baixeras, Núria Ballester, Rosa Castella, Eva Cuadras, Daniel Foj, Ruben Gil, Miguel González Suárez, Eva Güney, Emre, 1983- Hernández, Vanessa Martínez Aranda, Antonio Moreno, Ferran Moreno, Víctor Muixí, Laia Oliva Miguel, Baldomero Seguí, Miquel A. Sierra, Angels Urruticoechea, Ander Vidal, Noemí |
| author_facet | Martínez Aranda, Antonio Hernández, Vanessa Güney, Emre, 1983- Muixí, Laia Foj, Ruben Baixeras, Núria Cuadras, Daniel Moreno, Víctor Urruticoechea, Ander Gil, Miguel Oliva Miguel, Baldomero Moreno, Ferran González Suárez, Eva Vidal, Noemí Andreu, Xavier Seguí, Miquel A. Ballester, Rosa Castella, Eva Sierra, Angels |
| author_role | author |
| collection | Repositorio Digital de la UPF |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_f8aa9292eae7b1ab8b07805310e3cc2d |
| institution | Universitat Pompeu Fabra |
| instname_str | Universitat Pompeu Fabra |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositori.upf.edu:10230/25793 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| publisher | Impact Journals |
| publisherStr | Impact Journals |
| reponame_str | Repositorio Digital de la UPF |
| spelling | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies Martínez Aranda, Antonio Hernández, Vanessa Güney, Emre, 1983- Muixí, Laia Foj, Ruben Baixeras, Núria Cuadras, Daniel Moreno, Víctor Urruticoechea, Ander Gil, Miguel Oliva Miguel, Baldomero Moreno, Ferran González Suárez, Eva Vidal, Noemí Andreu, Xavier Seguí, Miquel A. Ballester, Rosa Castella, Eva Sierra, Angels Metàstasi Cervell Biomarkers Brain metastasis Breast cancer FN14 GRP94 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. 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 Impact Journals http://hdl.handle.net/10230/25793 http://dx.doi.org/10.18632/oncotarget.5471 |
| spellingShingle | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies Martínez Aranda, Antonio Metàstasi Cervell Biomarkers Brain metastasis Breast cancer FN14 GRP94 |
| status_str | publishedVersion |
| title | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| title_full | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| title_fullStr | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| title_full_unstemmed | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| title_short | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| title_sort | FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies |
| topic | Metàstasi Cervell Biomarkers Brain metastasis Breast cancer FN14 GRP94 |
| topic_facet | Metàstasi Cervell Biomarkers Brain metastasis Breast cancer FN14 GRP94 |
| url | http://hdl.handle.net/10230/25793 http://dx.doi.org/10.18632/oncotarget.5471 |