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


CONCLUSIONS
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.
Herath
Nirmitha I
NI
Leukaemia Foundation Research Unit, University of Queensland, Australia. Nirmitha.Herath@qimr.edu.au
Spanevello
Mark D
MD
Sabesan
Sabe
S
Newton
Tanya
T
Cummings
Margaret
M
Duffy
Shannon
S
Lincoln
Douglas
D
Boyle
Glen
G
Parsons
Peter G
PG
Boyd
Andrew W
AW
D018450:Disease Progression; D036382:Ephrin-A1 / Q000096:biosynthesis*; D036383:Ephrin-A2 / Q000096:biosynthesis*; D036386:Ephrin-A5 / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome
D036382:Ephrin-A1; D036383:Ephrin-A2; D036386:Ephrin-A5