Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer.
Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer.
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DOI：
10.1186/1479-5876-12-134
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发表时间：
2014-05-20
影响因子：
7.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wen N;Wang Y;Wen L;Zhao SH;Ai ZH;Wang Y;Wu B;Lu HX;Yang H;Liu WC;Li Y
Forkhead box M1（FOXM 1）是细胞分化和增殖的重要调节因子，在许多侵袭性人类癌中过表达。本研究的目的是检测FOXM 1在上皮性卵巢癌（EOC）中的表达水平，确定FOXM 1表达与患者生存率之间的关系，并研究FOXM 1在人类卵巢癌发展中的作用。在总共158个卵巢组织标本中进行了FOXM 1的免疫组织化学分析，所有标本均具有相关的临床结果数据。采用Kaplan-Meier法和考克斯比例风险分析将FOXM 1表达与临床病理变量、无进展生存期（PFS）和总生存期（OS）相关。采用pcDNA3.1-FOXM 1和FOXM 1 shRNA对卵巢癌细胞进行体外实验，以研究FOXM 1在卵巢癌细胞增殖、迁移和侵袭中的作用。FOXM 1水平升高与淋巴结转移有关（P = 0.009），但与年龄、FIGO分期、组织学分级和组织学类型无关。FOXM 1高表达患者的PFS（P = 0.0001）和OS（P < 0.0001）均低于FOXM 1低表达患者。此外，多变量分析表明FOXM 1阳性分别是PFS（P = 0.046）和OS（P = 0.022）的独立预后因素。过表达FOXM 1可增加HO-8910细胞基质金属蛋白酶-2（MMP-2）、MMP-9和血管内皮生长因子-A（VEGF-A）的表达和活性，促进癌细胞增殖、迁移和侵袭;而敲低FOXM 1可降低HO-8910 PM细胞MMP-2、MMP-9和VEGF-A的表达和活性，抑制癌细胞增殖、迁移和侵袭。我们的研究结果表明，FOXM 1表达可能在EOC的发展和进展中发挥重要作用。FOXM 1表达是影响EOC患者PFS和OS的一个潜在预后因素，可能成为EOC患者治疗的新靶点。
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. 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. 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. 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.
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影响因子：
3.7
作者：
Lok GT;Chan DW;Liu VW;Hui WW;Leung TH;Yao KM;Ngan HY
通讯作者：
Ngan HY
DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
21.3
作者：
Laoukili, J;Kooistra, MRH;Medema, RH
通讯作者：
Medema, RH
乙型肝炎病毒X蛋白诱导的FoxM1表达上调促进乙型肝炎病毒相关肝细胞癌的肿瘤转移并提示不良预后
影响因子：
25.7
作者：
Xia, Limin;Huang, Wenjie;Wu, Kaichun
通讯作者：
Wu, Kaichun
影响因子：
7.3
作者：
Chan, D. W.;Yu, S. Y. M.;Ngan, H. Y. S.
通讯作者：
Ngan, H. Y. S.