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

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.