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Open Access Highly Accessed Research article

Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival

Nirmitha I Herath1*, Mark D Spanevello1*, Sabe Sabesan1*, Tanya Newton2, Margaret Cummings4, Shannon Duffy1, Douglas Lincoln3, Glen Boyle2, Peter G Parsons2 and Andrew W Boyd14

Author Affiliations

1 Leukaemia Foundation Research Unit, University of Queensland, Australia

2 Melanoma Genomics, University of Queensland, Australia

3 Cancer and Population Studies, Queensland Institute of Medical Research, University of Queensland, Australia

4 Faculty of Health Sciences, University of Queensland, Australia

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BMC Cancer 2006, 6:144  doi:10.1186/1471-2407-6-144

Published: 1 June 2006

Abstract

Background

Increased expression of Eph receptor tyrosine kinases and their ephrin ligands has been implicated in tumor progression in a number of malignancies. This report describes aberrant expression of these genes in ovarian cancer, the commonest cause of death amongst gynaecological malignancies.

Methods

Eph and ephrin expression was determined using quantitative real time RT-PCR. Correlation of gene expression was measured using Spearman's rho statistic. Survival was analysed using log-rank analysis and (was visualised by) Kaplan-Meier survival curves.

Results

Greater than 10 fold over-expression of EphA1 and a more modest over-expression of EphA2 were observed in partially overlapping subsets of tumors. Over-expression of EphA1 strongly correlated (r = 0.801; p < 0.01) with the high affinity ligand ephrin A1. A similar trend was observed between EphA2 and ephrin A1 (r = 0.387; p = 0.06). A striking correlation of both ephrin A1 and ephrin A5 expression with poor survival (r = -0.470; p = 0.02 and r = -0.562; p < 0.01) was observed. Intriguingly, there was no correlation between survival and other clinical parameters or Eph expression.

Conclusion

These data imply that increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive tumor phenotype. The known functions of Eph/ephrin signalling in cell de-adhesion and movement may explain the observed correlation of ephrin expression with poor prognosis.