title: EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer.
abstract: The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization.
authors: Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, Linköping, Sweden.|Current address: CCRI, Children's Cancer Research Institute, St. Anna Kinderkrebsforschung e.V., Vienna, Austria.
authors: Anna-Maria
authors: AM
authors: Husa
authors: Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, Linköping, Sweden.
authors: Željana
authors: Ž
authors: Magić
authors: Bioinformatics Infrastructure for Life Sciences (BILS) and Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors: Malin
authors: M
authors: Larsson
authors: Department of Oncology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
authors: Tommy
authors: T
authors: Fornander
authors: Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, Linköping, Sweden.
authors: Gizeh
authors: G
authors: Pérez-Tenorio
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015331:Cohort Studies; D036342:Ephrins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D036183:Receptor, EphB2 / Q000235:genetics* / Q000378:metabolism; D036081:Receptors, Eph Family / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D036342:Ephrins; C586310:EPHB2 protein, human; D036183:Receptor, EphB2; D036081:Receptors, Eph Family
keywords: EPH family; EPHB2; TaqMan array; gene expression; protein expression