Overexpression of Forkhead Box O3a and Its Association With Aggressive Phenotypes and Poor Prognosis in Human Hepatocellular Carcinoma

Abstract

Objectives: Recent research has demonstrated that forkhead box O3a (FoxO3a) may function as an oncogenic transcription factor. We sought to validate the clinicopathologic significance of FoxO3a expression in hepatocellular carcinoma (HCC).Methods: Western blotting and immunohistochemistry were used to determine FoxO3a expression. In vitro cell proliferation and migration assays were performed in a HepG2 cell line.Results: FoxO3a was overexpressed in 121 (64.71%) cases of HCC. FoxO3a overexpression was associated with aggressive phenotypes of HCC, such as histologic grade (P < .001), stage (P = .031), and small vessel invasion (P < .001). FoxO3a overexpression was also correlated with poor disease-free survival in both univariate and multivariate survival analyses (P = .001 and P = .018, respectively). Downregulation of FoxO3a in a HepG2 cell line inhibited cell proliferation and migration.Conclusions: These results suggest a role for FoxO3a in HCC progression and support the potential use as a prognostic biomarker.