Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors

Sanz Pamplona, Rebeca; Aragüés Peleato, Ramón; Driouch, Keltouma; Martín, Berta; Oliva Miguel, Baldomero; Gil, Miguel; Boluda, Susana; Fernández, Pedro Luís; Martínez, Antonio; Moreno, Víctor; Acebes, Juan José; Lidereau, Rosette; Reyal, Fabien; Van De Vijver, Marc Joan; Sierra, Angels

Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors

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dc.contributor.author Sanz Pamplona, Rebecaca
dc.contributor.author Aragüés Peleato, Ramónca
dc.contributor.author Driouch, Keltoumaca
dc.contributor.author Martín, Bertaca
dc.contributor.author Oliva Miguel, Baldomeroca
dc.contributor.author Gil, Miguelca
dc.contributor.author Boluda, Susanaca
dc.contributor.author Fernández, Pedro Luísca
dc.contributor.author Martínez, Antonioca
dc.contributor.author Moreno, Víctorca
dc.contributor.author Acebes, Juan Joséca
dc.contributor.author Lidereau, Rosetteca
dc.contributor.author Reyal, Fabienca
dc.contributor.author Van De Vijver, Marc Joanca
dc.contributor.author Sierra, Angelsca
dc.date.accessioned 2015-12-15T15:35:57Z
dc.date.available 2015-12-15T15:35:57Z
dc.date.issued 2011
dc.description.abstract The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.ca
dc.description.sponsorship Supported by grants from the Spanish Ministry of Health and Consumer Affairs FIS/PI041937 and FIS/PI071245, by the European Commission MetaBre contract No. LSHC-CT-2004-506049, and by the Spanish Ministry of Education and Science SAF2004-0188-E. B.O. and R.A. acknowledge grants from the Spanish Ministry of Education and Science (MEC BIO2005-00533 and MCyT BIO2002-0369), and P.L.F. from the Marató-TV3, RETICC from Instituto Carlos III, and Xarxa de Bancs de Tumors de Catalunya
dc.format.mimetype application/pdfca
dc.identifier.citation Sanz-Pamplona R, Aragüés R, Driouch K, Martín B, Oliva B, Gil M et al. Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors. American journal of pathology. 2011;179(2):564-79. DOI: 10.1016/j.ajpath.2011.04.037ca
dc.identifier.doi http://dx.doi.org/10.1016/j.ajpath.2011.04.037
dc.identifier.issn 0002-9440
dc.identifier.uri http://hdl.handle.net/10230/25436
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof American journal of pathology. 2011;179(2):564-79
dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.ajpath.2011.04.037 that appeared in the journal American journal of pathology. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Ossos -- Càncerca
dc.subject.other Cervell -- Tumorsca
dc.subject.other Regulació genèticaca
dc.title Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumorsca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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