Epigenetic silencing of EphAI expression in colorectal cancer is correlated with poor survival

Aberrant expression of Eph and ephrin proteins has well-established functions in oncogenesis and tumour progression. We describe EphAI expression in 6 colorectal cancer (CRC) cell lines, 18 controls and 125 CRC specimens. In addition, a well-characterised cohort of 53 paired normal colon and CRCs was also assessed. Expression of EphAI mRNA was assessed by quantitative real-time PCR and correlated with protein expression by flow cytometry, immunoprecipitation, western blotting and immunohistochemistry, Significant upregulation (2- to 10-fold) of EphAI was seen in over 50% of cases (P = 0.005) whereas many of the remainder showed downregulation of EphAI. Intriguingly, EphAI over-expression was more prevalent in stage II compared to stage III CRCs (P = 0.02). Low EphAI expression significantly correlated with poor survival (P = 0.02). Epigenetic silencing appeared to explain the loss of EphAI expression as methylation of the EphAI CpG island strongly correlated with low EphAI expression (P