title: Increased expression of Forkhead box M1 transcription factor is associated with clinicopathological features and confers a poor prognosis in human hepatocellular carcinoma.
abstract: OBJECTIVE
  Forkhead Box M1 (FoxM1) is a proliferation-specific transcription factor. In this study, we aimed to elucidate the clinicopathological and prognostic values of FoxM1 expression in human hepatocellular carcinoma (HCC) and correlate FoxM1 expression with various etiologies of liver diseases. We also investigated its therapeutic value in HCC.
  
  
  METHODS
  We investigated the expression of FoxM1 in tumor tissues and adjacent non-tumor tissues of 79 Japanese HCC patients by quantitative real-time reverse transcription-polymerase chain reaction analysis. Depletion by siRNA or specific inhibition by siomycin A were also used to investigate the effect of FoxM1 inhibition on stem-like features of human HCC cells.
  
  
  RESULTS
  Quantitative real-time reverse transcription-polymerase chain reaction analysis showed that tumor tissues displayed an approximately 14-fold increase in FoxM1 expression 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 FoxM1 in tumor tissues was associated with serum α-fetoprotein level, maximum tumor size, histological grade, TNM staging, and portal involvement. Kaplan-Meier analysis indicated that the high FoxM1 expression (≥median) group had a poor prognosis compared with the low FoxM1 expression (<median) group. Using multivariate analysis, the expression of FoxM1 in tumor tissues was shown to be an independent prognostic factor that affected overall survival and disease-free survival. Furthermore, FoxM1 inhibition by siRNA or siomycin A reduced spheroid colony formation of HCC cells in vitro.
  
  
  CONCLUSIONS
  Our data suggest that FoxM1 might be a prognostic biomarker and a promising therapeutic target for HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Egawa
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kizu
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Kunimaro
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.|Department of Molecular Biochemistry and Clinical Investigation, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Chatani
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Hamano
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Hayato
authors.identifier: http://orcid.org/0000-0003-2488-7315
authors.initials: H
authors.lastname: Hikita
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
keywords: Forkhead box M1 transcription factor; hepatocellular carcinoma; prognostic biomarker; siomycin A