title: Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer.
abstract: BACKGROUND
  The Forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. The purpose of this study was to examine the expression levels of FOXM1 in epithelial ovarian cancer (EOC), to identify the relationship between FOXM1 expression and patient survival, and to investigate the role of FOXM1 in human ovarian cancer development.
  
  
  METHODS
  Immunohistochemical analysis for FOXM1 was performed in a total of 158 ovarian tissue specimens, all with linked clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis were used to relate FOXM1 expression to clinicopathological variables and to progression-free survival (PFS) and overall survival (OS). In vitro studies were performed to determine the function of FOXM1 in cell proliferation, migration and invasion in EOC cells using pcDNA3.1-FOXM1 and FOXM1 shRNA.
  
  
  RESULTS
  Elevated FOXM1 levels were associated with lymph node metastasis (P = 0.009), but not with age, FIGO stage, histological grade and histological type. Patients with high expression of FOXM1 had poorer PFS (P = 0.0001) and OS (P < 0.0001) than patients with low expression of FOXM1. Furthermore, multivariate analyses indicated that FOXM1 positivity was an independent prognostic factor for PFS (P = 0.046) and OS (P = 0.022), respectively. Overexpression of FOXM1 increased expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor-A (VEGF-A), and cancer cell proliferation, migration and invasion of HO-8910 cells, whereas knockdown of FOXM1 reduced expression and activity of MMP-2, MMP-9 and VEGF-A, and cancer cell proliferation, migration and invasion of HO-8910 PM cells.
  
  
  CONCLUSIONS
  Our results suggest that FOXM1 expression is likely to play important roles in EOC development and progression. FOXM1 expression is a potential prognostic factor for PFS and OS, and it could be a novel treatment target in EOC patients.
authors.affiliation: Department of Stomatology, The General Hospital of Chinese PLA, Beijing 100853, China. wenning301@gmail.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Wen
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Zhao
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Ai
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Huai-Xiu
authors.initials: HX
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D000077216:Carcinoma, Ovarian Epithelial; D017931:DNA Primers; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors