Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer

Background: The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in not only cell motility, cell adhesion, and apoptosis, but also in various cell signaling pathways. Phosphorylation at Thr-567 and Tyr-353 are key regulatory events in the transition of the dormant to active form of ezrin. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC). Methods: Ezrin and p-ezrin protein expressions were examined by immunohistochemistry in 150 NSCLC and adjacent non-tumor tissues and 14 normal lung tissues. qRT-PCR was used to determine ezrin mRNA expression levels in fresh tissues. The correlations between overexpression of ezrin and p-ezrin and the clinicopathological features of NSCLC were analyzed. The survival rates were calculated by the Kaplan-Meier method for 108 NSCLC cases. Results: Ezrin and ezrin^Thr-567 proteins showed cytosolic and membranous staining patterns; however, ezrin^Tyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrin^Thr-567, and ezrin^Tyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrin^Thr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrin^Thr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrin^Thr-567 were associated with shortened survival time for patients with early stage NSCLC. Conclusions: Ezrin and p-ezrin, especially ezrin^Thr-567, may prove to be useful as a novel prognostic biomarker of NSCLC.