Prognostic value of high FoxC2 expression in resectable non-small cell lung cancer, alone or in combination with E-cadherin expression

Abstract

Background: FoxC2 is an epithelial-mesenchymal transition (EMT) regulator which induces metastasis. The purpose of this study is to assess the prognostic value of FoxC2 expression in non-small cell lung cancer (NSCLC), alone or in combination with E-cadherin expression. Methods: A retrospective study was conducted using immunohistochemistry to investigate FoxC2 and E-cadherin expression in a cohort of 309 patients with surgically resected NSCLCs. The prognostic value of FoxC2 and E-cadherin on overall survival (OS) and recurrence-free survival (RFS) was determined by Kaplan-Meier analysis and Cox proportional hazard models. Results: High FoxC2 expression was detected in 26.5 % of tumors, and significantly correlated with tobacco use (p = 0.047), adenocarcinoma (p = 0.008) and nodal involvement (p < 0.001). Univariate analysis revealed its association with OS (p = 0.036) and RFS (p = 0.011). By multivariate analysis, high FoxC2 expression lost its significance as an independent predictor of recurrence (p = 0.077), while TNM stage, nodal status and the presence of high FoxC2 and impaired E-cadherin expression retained independent prognostic significance in relation to both OS and RFS. Subset analyses indicated that high FoxC2 expression was significantly associated with disease outcome in node-positive, but not in node-negative patients. Conclusion: Evaluation of FoxC2 expression, alone or in combination with E-cadherin expression, may help to stratify NSCLC patients for risk of disease progression, pointing to this EMT regulator as a potential prognostic marker.