Abstract
BackgroundThe 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.MethodsImmunohistochemical 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.ResultsElevated 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.ConclusionsOur 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.
Highlights
The Forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas
Multivariate Cox analysis showed that Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and FOXM1 expression were independent risk factors that influenced the prognosis of epithelial ovarian cancer (EOC) (Table 2 and 3)
In summary, the present study showed that FOXM1 overexpression was associated with lymph node status and poor patient survival in EOC
Summary
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. Ovarian cancer is the leading cause of death among gynecologic malignancy in the world, with increasing incidence recently in China [1]. Epithelial ovarian cancer (EOC) account for nearly 70% of all ovarian malignant diseases. There is an urgent requirement to identify extra prognostic indicators and to improve on current understanding of the molecular mechanisms underlying EOC. It would be very helpful for patients with advanced disease
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