Abstract
BackgroundThe 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).MethodsEzrin 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.ResultsEzrin and ezrinThr-567 proteins showed cytosolic and membranous staining patterns; however, ezrinTyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrinThr-567, and ezrinTyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrinThr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrinThr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrinThr-567 were associated with shortened survival time for patients with early stage NSCLC.ConclusionsEzrin and p-ezrin, especially ezrinThr-567, may prove to be useful as a novel prognostic biomarker of NSCLC.
Highlights
The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in cell motility, cell adhesion, and apoptosis, and in various cell signaling pathways
We found that ezrin and p-ezrin are frequently upregulated in non-small cell lung carcinoma (NSCLC) compared with the normal counterparts, and are related with the poor differentiation and late clinical stage of NSCLC
We found that p-ezrin exhibited cytosolic and membranous staining patterns in NSCLC, and the percentages of ezrinThr-567 and ezrinTyr-353 expression were significantly higher in NSCLC than in adjacent non-tumor tissues and normal tissue counterparts (P < 0.01)
Summary
The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in cell motility, cell adhesion, and apoptosis, and in various cell signaling pathways. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC). 85% of lung cancers are non-small cell lung cancer (NSCLC) [2]. Ezrin is a member of the ezrin-radixinmoesin (ERM) family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton [8]. In its inactive form, ezrin is located in the cytoplasm and its Cterminal domain, an F-actin-binding site, is masked by the N-terminal domain of ezrin or other ERM family member proteins. Once ezrin is activated by threonine and tyrosine phosphorylation, it assumes an active form, in which its N-
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