Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma

Abstract

Abstract. the aim of this study was to detect the expression of the Forkhead box M1 (FoXM1) protein in human hepatocellular carcinoma (Hcc) and to associate FoXM1 expression with clinicopathological features of the patients, and predict the prognosis of patients with FoXM1 expression. surgical tissue specimens from 151 Hcc patients were subjected to a tissue microarray construction and immunohistochemistry analysis of FoXM1 and the proliferation marker proliferating cell nuclear antigen (pcnA). the data showed that the FoXM1 protein was expressed in 59.3% of the Hcc tissues, which was significantly higher compared to that of the surrounding non-tumorous tissues (23.8%; p<0.001). Moreover, FoXM1 expression was positively correlated with the labeling index of pcnA (p<0.001) in Hcc and with aggressive tumor phenotypes, such as larger tumor size, multiple tumors, bilobar involvement, poor tumor cell differentiation, advanced stage and macrovascular invasion (p<0.05). In addition, Hcc patients with FoXM1-positive tumors had a poorer recurrencefree and overall survival after hepatectomy than those with FoXM1-negative tumors. Multivariate cox regression analysis demonstrated that FoXM1 expression was an independent predictor of unfavorable outcome (p<0.05). the data from the current study suggest that FoXM1 may play an important role in Hcc progression and could be further evaluated as a prognostic biomarker and potential therapeutic target.

Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein

“…Its over-expression coincides with high-grade progression in almost all types of cancers, including those in breast12, liver34, lung56, prostate78, pancreas910, ovary11, brain12, nasopharynx13, esophagus14, and also in certain leukemia15. Moreover, a study that analyzed 18,000 human tumors with outcomes for 39 different malignancies identified over-expression of FoxM1 as a major predictor for poor prognosis16.…”

Immunotherapy based on dendritic cells pulsed with CTPFoxM1 fusion protein protects against the development of hepatocellular carcinoma

“…Thirdly, FoxM1 plays an essential role in HCC cell migration, invasion, as well as liver cancer progression and in cancer cells with stem cell features [15, 22]. Fourthly, clinicopathologic studies suggest that FoxM1 expression correlated with poorly-differentiated HCC tumors with intrahepatic metastasis, which is a leading cause of post-surgical recurrence and low survival rate [20, 29]. Finally, silencing of FoxM1 expression could inhibit human hepatocellular carcinoma growth [30], and FoxM1 has been reported an underlying therapeutic target because it can be presented to cell surface by tumor cells [31].…”

“…Overexpression of FoxM1 in various tumors indicates a strong dependence of the tumor cells on FoxM1 expression because of an integral role of FoxM1 in tumorigenesis [15–19]. Previous studies have shown that FoxM1 was essential for development of HCC, and overexpression of FoxM1 was associated with aggressive tumor features and poor prognosis [20]. In fact, FoxM1 could induce an epithelial-mesenchymal-like transition phenotype in HCC cells, increase cell migration, and induce premetastatic niche at the distal organ of metastasis [21, 22].…”

SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells

“…Studies have confirmed that FOXM1 expression levels correlate with poor prognosis [23,24]. Moreover, amplifications of FOXM1 gene have been demonstrated in several tumors such as hepatocellular cancer, pancreatic cancer, and glioblastoma multiforme tumors [13,25,26,27]. Therefore, targeting FOXM1 (the relay center for cancer development and a potential prognostic marker) holds a promising therapeutic intervention.…”