Overexpression of FOXM1 Is Associated With Poor Prognosis and Clinicopathologic Stage of Pancreatic Ductal Adenocarcinoma

Ji, Xia; Wang, Hua; Liu, Liang; Peng, Baogang; Zhaofeng, Wu; Chen, Lianzhou; Xue, Ling; Li, Zhi; Li, Wen

doi:10.1097/mpa.0b013e31823bcef2

Cited by 71 publications

(52 citation statements)

References 25 publications

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“…Dual luciferase assays revealed that STAT3 is directly targeted by miR130b, which was further confirmed by the inverse expression of miR-130b and STAT3 in pancreatic cancer specimens [66]. Recently, another transcription factor named FOXM1 is perceived to play an important role in pancreatic cancer progression [67]. Notably, FOXM1 overexpression is responsible for acquisition of the EMT and CSC phenotypes, which is mediated in part by the regulation of miR-200b expression [68].…”

Section: • Crosstalk Between Mirnas and Transcription Factors In Pancrementioning

confidence: 87%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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Pancreatic cancer is a devastating malignancy that ranks as the fourth leading cause of cancerrelated deaths worldwide. Dismal prognosis is mainly attributable to limited knowledge of the molecular pathogenesis of the disease. miRNAs have been found to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by regulating important signaling pathways, such as the KRAS and Notch pathways. Moreover, the effect of miRNAs on regulating cell cycle events and expression of transcription factors has gained a lot of attention. Recent studies have highlighted the application of miRNAs as biomarkers and therapeutic tools. The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics. KEYWORDS• antisense oligonucleotides • miRNAs • pancreatic cancer Pancreatic cancer overview Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic neoplasms and accounts for greater than 85% of the clinical cases [1]. The disease develops via acinar-ductal metaplasia and neoplastic precursor lesions [2]. In the USA alone, 48,960 new cases of pancreatic cancer were expected to occur in 2015, with an estimated 40,560 deaths, about the same number in women (19,850) as in men (20,710). Over 96% are cancers arising from exocrine pancreas. Endocrine carcinomas are often diagnosed at a younger age and exhibit a better prognosis. From 2007 to 2011, mortality rates increased slightly by 0.3% per year. For all stages combined, the 1-and 5-year relative survival rates are 28 and 7%, respectively. For the small percentage of people diagnosed with local disease (9%), the 5-year survival is 26%, while more than half of patients (53%) are diagnosed at a late stage for which 1-and 5-year survival rates reach 15 and 2%, respectively [3]. These numbers are a staggering example of the poor prognosis associated with PDAC.While new therapeutic options are emerging for nonhematologic malignancies, molecular-targeted therapies for pancreatic cancer have failed to make any positive impact on patient survival. In 1993, the Nobel Prize-winning discovery of small interference RNAs (siRNAs) led to an outburst of knowledge on RNA interference and gene regulation [4]. Since then, thousands of research studies have described the functional role of small noncoding RNAs, named miRNAs, in a vast panel of human pathologies. In 2002, a small genomic region in chromosome 13q14 comprising miR-15a and miR-16-1 genes was found to be commonly deleted in chronic lymphocytic leukemia, For reprint orders, please contact: reprints@futuremedicine.com

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Section: • Crosstalk Between Mirnas and Transcription Factors In Pancrementioning

confidence: 87%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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“…Some studies also showed the same results. Xia et al found that a high level of expression of FoxM1 was significantly correlated with clinical staging (P = 0.00), lymph node metastasis (P = 0.01), and histological differentiation (P = 0.02) in pancreatic ductal adenocarcinoma (Xia et al, 2012). Chu et al revealed that high FoxM1 expression was closely correlated with the presence of lymph node metastasis, incidence of liver metastasis, and advanced TNM stage in colorectal cancer (Chu et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The staining score was categorized into two groups as weak/negative staining (score < 4) and strong staining (score ≥ 4) (Liu et al, 2011;Xia et al, 2012). The highest labeling score among the three tissue sections was entered for statistical analyses.…”

Section: Immunohistochemical Staining For Foxm1mentioning

confidence: 99%

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

Wu²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: Predictive biomarkers for lung cancer recurrence after curative tumor resection remain unclear. This study set out to assess the role of FoxM1 in the recurrence of non-small cell lung cancer. Methods: Immunohistochemistry for FoxM1 expression was performed on paraffin-embedded tumor tissues from 165 NSCLC patients. Association of FoxM1 expression with clinicopathological parameters and disease free survival were evaluated. Results: Our results indicated FoxM1 expression to be significantly associated with poorer tissue differentiation (P =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced tumor stage (P <0.01), and poorer disease free survival (P <0.01). Multivariable analysis showed that FoxM1 expression increased the hazard of recurrence (hazard ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1 is an independent and significant predictor of lung cancer recurrence. Conclusion: Therefore, FoxM1 is an independent risk factor for recurrence of NSCLC. Elevated FoxM1 expression could be used as an indicator of poor disease free survival.

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“…Elevated expression of FOXM1 has been detected in a wide range of human tumors and has been implicated in cellular transformation, tumor initiation and progression (7). Accumulating evidence demonstrates that increased expression of FOXM1 is associated with poor prognosis in various types of cancers (8)(9)(10)(11), including MB (12). Furthermore, previous studies have shown that FOXM1 mediates resistance to a diverse spectrum of anticancer drugs in breast cancer (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

et al. 2013

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Abstract. Medulloblastoma (MB) is the most common malignant brain tumor in children and is highly invasive and metastatic. Despite recent advances, most MB patients suffer significant therapy-related morbidity, and the survival rate for patients with metastatic MB remains unsatisfactory. Altered expression of FOXM1 has been detected in many types of cancers, and the inhibition of FOXM1 has been studied as a cancer therapy. In the present study, we evaluated the impact of the inhibition of FOXM1 by thiostrepton in Daoy MB cells. Cells were treated with different concentrations of thiostrepton alone or in combination with cisplatin. Cell viability was measured with CCK-8 assays, and cell cycle distribution and apoptosis were assessed by flow cytometric analysis. Changes in protein expression were examined by western blotting. RNAi experiments were performed using siRNA oligonucleotides. The invasion and migration studies were performed using 8-µm Transwell plates. Inhibition of FOXM1 by thiostrepton significantly decreased MB cell proliferation. Cell arrest at the G2/M phase and apoptosis were significantly increased in MB cell lines that were treated with thiostrepton or transfected with siRNA. Thiostrepton decreased the IC 50 value of cisplatin for MB treatment by enhancing cisplatininduced apoptosis. Thiostrepton also decreased cell invasion and migration, which are crucial steps for tumor progression. Our data suggest that targeting FOXM1 with small-molecule inhibitors results in potent antitumor activity and chemosensitizing effects in human medulloblastoma cells.

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Overexpression of FOXM1 Is Associated With Poor Prognosis and Clinicopathologic Stage of Pancreatic Ductal Adenocarcinoma

Abstract: Our finding indicates that FoxM1 could be used as prognostic molecular marker and therapeutic target for PDA.

Cited by 71 publications

References 25 publications

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

Inhibition of FOXM1 by thiostrepton sensitizes medulloblastoma to the effects of chemotherapy

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