Overexpression of 14-3-3ζ in lung tissue predicts an improved outcome in patients with lung adenocarcinoma.

Abstract

One of the factors limiting the survival rate of patients with lung cancer is the high risk for recurrence following surgical resection. Previous studies indicate that 14-3-3ζ is a central cellular hub protein that regulates multiple signaling pathways involved in cancer progression. The present study evaluated the prognostic significance of 14-3-3ζ in patients with lung adenocarcinoma. The expression of 14-3-3ζ and E-cadherin, an important protein involved in the epithelial-mesenchymal transition, was evaluated by immunohistochemistry in lung tumor tissues and adjacent normal lung tissues resected from 123 patients with lung adenocarcinoma. The correlation between the two proteins, their association with clinicopathological features and their prognostic significance were subsequently analyzed. Within these parameters, an overall survival (OS) prediction model was constructed using multivariate Cox proportional hazards regression. The expression of 14-3-3ζ was upregulated in lung adenocarcinoma, in contrast to E-cadherin, which was downregulated in lung adenocarcinoma tissues compared with normal tissues. In addition, the expression of 14-3-3ζ was positively correlated with that of E-cadherin (r=0.256, P=0.012) and differentiation (P<0.001). Increased E-cadherin expression was indicative of smaller tumor size and greater differentiation, and the overexpression of 14-3-3ζ and E-cadherin were associated with longer OS (P=0.010 and P=0.006, respectively). Finally, a multivariate analysis revealed that TNM stage and 14-3-3ζ were independent prognostic indicators (P<0.001 and P=0.026, respectively). 14-3-3ζ may function as a tumor suppressor associated with E-cadherin upregulation and could be used as a prognostic biomarker for resected lung adenocarcinoma. These findings provide a novel insight on potential intervention strategies for patients with lung cancer.