Characterization Of FOXM1 Expression In Hepatocellular Carcinoma: A Clinicopathologic And Molecular Study

Aims: To investigate the clinical significance of Forkhead box M1 (FOXM1) expression in human hepatocellular carcinoma (HCC).Methods: immunohistochemistry was applied to detect FOXM1 expression in 38 resected liver tissues from HCC patients. microparticle enzyme immunoassay was employed to measureα-fetoprotein (AFP) from both HCC patients serum and cell culture media.Results: FOXM1 overexpression was observed in 25/38 (65.8%) HCC specimens, and FOXM1 expression was more frequently detected in the poorly-differentiated HCC tissues than in the well-differentiated ones (P=0.002). Moreover, HCC patients who were positive for FOXM1 staining showed a nearly doubled average serumα-fetoprotein (AFP) secretion as compared with those of the patients with negative FOXM1. Furthermore, FOXM1 suppression by either Thiostrepton or SiRNA-FOXM1 in both HepG2 and HepG2.2.15 human HCC cells led to significant inhibition of AFP secretion. However, poor differentiation was demonstrated to be the only independent poor prognostic factor among all the evaluated clinicopathologic parameters (P=0.041). Kaplan-Meier survival curves demonstrated no significant difference between the survival times of the patients with positive FOXM1 and those with negative FOXM1 (P=0.242), while multivariate analysis revealed HBV infection and metastasis being two independent poor prognostic factors (P=0.005 and 0.000, respectively).Conclusions: FOXM1 expression was associated with differentiation but not an aggressive clinical course in a Chinese HCC cohort. A possible novel role of FOXM1 in the regulation of AFP production during human hepatocarcinogenesis deserves further investigation.