Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome
Identifieur interne : 004680 ( Ncbi/Checkpoint ); précédent : 004679; suivant : 004681Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome
Auteurs : Dana M. Brantley-Sieders ; Aixiang Jiang [États-Unis] ; Krishna Sarma ; Akosua Badu-Nkansah [États-Unis] ; Debra L. Walter ; Yu Shyr [États-Unis] ; Jin Chen [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated
Url:
DOI: 10.1371/journal.pone.0024426
PubMed: 21935409
PubMed Central: 3174170
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated <italic>eph</italic>
and <italic>ephrin</italic>
expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between <italic>ephA2</italic>
, <italic>ephA4</italic>
, <italic>ephA7</italic>
, <italic>ephB4</italic>
, and <italic>ephB6</italic>
and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between <italic>ephrin</italic>
ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.</p>
</div>
</front>
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<author><name sortKey="Filho, Up" uniqKey="Filho U">UP Filho</name>
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