EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer
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Anna-Maria Husa1,2, Željana Magić1, Malin Larsson3, Tommy Fornander4, Gizeh Pérez-Tenorio1
1Department of Clinical and Experimental Medicine, Division of Oncology, Linköping University, Linköping, Sweden
2Current address: CCRI, Children’s Cancer Research Institute, St. Anna Kinderkrebsforschung e.V., Vienna, Austria
3Bioinformatics Infrastructure for Life Sciences (BILS) and Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden
4Department of Oncology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
Gizeh Pérez-Tenorio, e-mail: [email protected]
Keywords: EPHB2, EPH family, TaqMan array, gene expression, protein expression
Received: July 03, 2015 Accepted: January 23, 2016 Published: February 8, 2016
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.
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