Abstract
The Eph receptor/ephrin ligand system is the largest family of tyrosine kinase with signaling modality through cell to cell adhesion. Eph/ephrin is involved in malignant phenotype such as cell proliferation, migration, and invasion in cancer cells. Although the functions of the Eph receptors in glioblastoma have been elucidated, little is known on ephrin ligands, especially ephrin-A2. Here, we analyze the expression of ephrin-A2 in gliomas using surgical specimens. The expression level of ephrin-A2 mRNA in 14 normal brains and glioma (WHO grade II 13, III 10, and IV 40) was measured by quantitative real-time PCR. Ephrin-A2 expression level was significantly lower in glioblastoma than in normal brain (p= 0.0127). When we divided the glioblastoma cases into high and low ephrin-A2 expression groups based on the median value, the overall survival (OS) was significantly longer in the high expression group compared with the low expression group (p= 0.034, median 24.0 and 14.0 months, respectively). Furthermore, multivariate analysis of factors related to OS with ephrin-A2 expression level and general prognostic factors (age, sex, preoperative KPS, surgical resection rate, radiochemotherapy, IDH1 mutation, MGMT promotor methylation) was performed. Ephrin-A2 expression level (p= 0.039), MGMT promotor methylation (p= 0.0001), and surgical resection rate (p= 0.017) were identified as independent prognostic factors. Taken together, ephrin-A2 is an independent favorable prognostic factor in glioblastoma.