TY - JOUR
T1 - Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors
AU - Sanz-Pamplona, Rebeca
AU - Aragüés, Ramón
AU - Driouch, Keltouma
AU - Martín, Berta
AU - Oliva, Baldo
AU - Gil, Miguel
AU - Boluda, Susana
AU - Fernández, Pedro L.
AU - Martínez, Antonio
AU - Moreno, Víctor
AU - Acebes, Juan J.
AU - Lidereau, Rosette
AU - Reyal, Fabien
AU - van de Vijver, Marc J.
AU - Sierra, Angels
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.ajpath.2011.04.037
DO - https://doi.org/10.1016/j.ajpath.2011.04.037
M3 - Article
C2 - 21708117
SN - 0002-9440
VL - 179
SP - 564
EP - 579
JO - American journal of pathology
JF - American journal of pathology
IS - 2
ER -