Increased FoxM1 expression is associated with clinicopathological features and confers a poor prognosis in human hepatocellular carcinoma.

Aims Forkhead Box M1 ( FoxM1) is a proliferation-specific transcription factor. In this study, we aimed to elucidate the clinicopathological and prognostic values of FoxM1expression in human hepatocellular carcinoma (HCC) and correlate FoxM1expression with various etiologies of liver diseases. We also investigated its therapeutic value in HCC. Methods We investigated the expression of FoxM1in tumor tissues and adjacent non-tumor tissues of 79 Japanese HCC patients by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Depletion by small-interfering RNA (siRNA) or specific inhibition by Siomycin A were also used to investigate the effect of FoxM1inhibition on stem-like features of human HCC cells. Results qRT-PCR analysis showed that tumor tissues displayed an approximately 14-fold increase in FoxM1expression compared with adjacent non-tumor tissues. Interestingly, the expression levels of FoxM1in tumor tissues did not depend on the etiology of liver disease. The expression of FoxM1in tumor tissues was associated with serum AFP level, maximum tumor size, histological grade, AJCC/UICC TNM staging, and portal involvement. Kaplan-Meier analysis demonstrated that the high FoxM1expression (≥ median) group had a poor prognosis compared with the low FoxM1expression (< median) group. Using multivariate analysis, the expression of FoxM1in tumor tissues was shown to be an independent prognostic factor that affected overall survival and disease-free survival. Furthermore, FoxM1inhibition by siRNA or Siomycin A reduced spheroid colony formation of HCC cells in vitro. Conclusions Our data suggest that FoxM1might be a prognostic biomarker and a promising therapeutic target for HCC.