Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients

FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to strati...

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Autores: Martínez-Aranda, Antonio, Hernández, Vanessa, Moreno, Ferran, Baixeras, Núria, Cuadras, Daniel|||0000-0001-8780-1764, Urruticoechea, Ander|||0000-0003-0359-3641, Gil-Gil, Miguel|||0000-0003-1380-2718, Vidal, Noemí|||0000-0002-2852-6667, Andreu, Xavier, Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746, Ballester Alabau, Rosa María, Castellà Fernández, Eva, Sierra, Angels
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186400
Acceso en línea:https://ddd.uab.cat/record/186400
https://dx.doi.org/urn:doi:10.3389/fonc.2017.00283
Access Level:acceso abierto
Palabra clave:Biomarkers
Brain metastasis
Breast cancer
FN14
GRP94
Prediction
Prevention
Prognosis
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spelling Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer PatientsFN14 and GRP94 from Diagnosis to ProphylaxisMartínez-Aranda, AntonioHernández, VanessaMoreno, FerranBaixeras, NúriaCuadras, Daniel|||0000-0001-8780-1764Urruticoechea, Ander|||0000-0003-0359-3641Gil-Gil, Miguel|||0000-0003-1380-2718Vidal, Noemí|||0000-0002-2852-6667Andreu, XavierSeguí Palmer, Miguel Ángel|||0000-0002-5103-6746Ballester Alabau, Rosa MaríaCastellà Fernández, EvaSierra, AngelsBiomarkersBrain metastasisBreast cancerFN14GRP94PredictionPreventionPrognosisFN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.Universitat Autònoma de Barcelona 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186400https://dx.doi.org/urn:doi:10.3389/fonc.2017.00283reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-530open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1864002026-06-06T12:50:31Z
dc.title.none.fl_str_mv Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
FN14 and GRP94 from Diagnosis to Prophylaxis
title Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
spellingShingle Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
Martínez-Aranda, Antonio
Biomarkers
Brain metastasis
Breast cancer
FN14
GRP94
Prediction
Prevention
Prognosis
title_short Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
title_full Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
title_fullStr Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
title_full_unstemmed Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
title_sort Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients
dc.creator.none.fl_str_mv Martínez-Aranda, Antonio
Hernández, Vanessa
Moreno, Ferran
Baixeras, Núria
Cuadras, Daniel|||0000-0001-8780-1764
Urruticoechea, Ander|||0000-0003-0359-3641
Gil-Gil, Miguel|||0000-0003-1380-2718
Vidal, Noemí|||0000-0002-2852-6667
Andreu, Xavier
Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746
Ballester Alabau, Rosa María
Castellà Fernández, Eva
Sierra, Angels
author Martínez-Aranda, Antonio
author_facet Martínez-Aranda, Antonio
Hernández, Vanessa
Moreno, Ferran
Baixeras, Núria
Cuadras, Daniel|||0000-0001-8780-1764
Urruticoechea, Ander|||0000-0003-0359-3641
Gil-Gil, Miguel|||0000-0003-1380-2718
Vidal, Noemí|||0000-0002-2852-6667
Andreu, Xavier
Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746
Ballester Alabau, Rosa María
Castellà Fernández, Eva
Sierra, Angels
author_role author
author2 Hernández, Vanessa
Moreno, Ferran
Baixeras, Núria
Cuadras, Daniel|||0000-0001-8780-1764
Urruticoechea, Ander|||0000-0003-0359-3641
Gil-Gil, Miguel|||0000-0003-1380-2718
Vidal, Noemí|||0000-0002-2852-6667
Andreu, Xavier
Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746
Ballester Alabau, Rosa María
Castellà Fernández, Eva
Sierra, Angels
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Biomarkers
Brain metastasis
Breast cancer
FN14
GRP94
Prediction
Prevention
Prognosis
topic Biomarkers
Brain metastasis
Breast cancer
FN14
GRP94
Prediction
Prevention
Prognosis
description FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/186400
https://dx.doi.org/urn:doi:10.3389/fonc.2017.00283
url https://ddd.uab.cat/record/186400
https://dx.doi.org/urn:doi:10.3389/fonc.2017.00283
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-530
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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