Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithe
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RESEARCH
Open Access
Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer Ning Wen1*†, Yu Wang1,2†, Li Wen1†, Shu-Hua Zhao3†, Zhen-Hua Ai2, Yi Wang4, Bo Wu4, Huai-Xiu Lu5, Hong Yang3, Wen-Chao Liu2 and Yu Li4*
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. Keywords: Ovarian cancer, FOXM1, Prognosis, Proliferation, Migration, Invasion
* Correspondence: [email protected]; [email protected] † Equal contributors 1 Department of Stomatology, The General Hospital of Chinese PLA, Beijing 100853, China 4 Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi’an 710032, China Full list of author information is available at the end of the article © 2014 Wen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction i
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