Abstract
BackgroundForkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies. However, little research has been done to investigate its clinical significance in gastric cancer.MethodsWe examined the expression of FOXM1 in 103 postoperational gastric cancer tissues and 5 gastric cell lines by immunohistochemistry and western blot analysis respectively. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed. Moreover, the association of FOXM1 expression and chemosensitivity to docetaxel in gastric cancer cells was further explored.ResultsOur study demonstrated that the level of FOXM1 expression was significantly higher in gastric cancer than in para-cancer tissues (P < 0.001) and normal gastric cell lines (P = 0.026). No significant association was found between FOXM1 expression and any clinical pathological features (P > 0.1). FOXM1 amplification was identified as an independent prognostic factor in gastric cancer (P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P = 0.004), pT3-4 (P = 0.003) or pIII-IV (P = 0.001). Additionally, shown to mediate docetaxel resistance in gastric cancers by our research, FOXM1 was revealed to alter microtubule dynamics in response to the treatment of docetaxel, and the drug resistance could be reversed with FOXM1 inhibitor thiostrepton treatment.ConclusionsFOXM1 can be a useful marker for predicting patients’ prognosis and monitoring docetaxel response, and might be a new therapeutic target in docetaxel resistant gastric cancer.
Highlights
Forkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies
IHC results revealed that the level of FOXM1 expression was significantly higher in gastric cancer than in para-cancer tissues (Table 1, P < 0.001), indicating that FOXM1 was commonly overexpressed in human gastric cancers
To further confirm that results in vitro, we investigated the level of FOXM1 expression in benign and malignant human gastric cell lines by western blot analysis
Summary
Forkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies. Most patients present with metastatic or unresectable disease at the time of diagnosis [2] For these surgically unfit but medically fit patients, palliative chemotherapy is the main. In current research, FOXM1 amplification was reported to confer primary resistance of gefitinib in nonsmall cell lung cancer (NSCLC) and acquired paclitaxel resistance in breast cancer, showing implications in resistance to chemotherapy strongly [24,25]. These results suggested that FOXM1 may play an important role in progression of human cancers and may be associated with the resistance to docetaxel. FOXM1 has been revealed to mediate promotion of human gastric cancer angiogenesis, growth, and metastasis [26], the clinical significance of FOXM1 overexpression in gastric cancer is still little explored yet
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