Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel

Journal of Translational Medicine

Jun Liang²  Yasai Yao²  Shihai Liu³  Ruyong Yao³  Bin Liu¹  Wensheng Qiu²  Xiaoxiao Li² 

[1] Department of Nuclear Medicine, Affiliated Hospital of Medical College Qingdao University, Qingdao, China;Department of Oncology, Affiliated Hospital of Medical College Qingdao University, 16 Jiangsu Road, Qingdao 266003, China;Central Laboratory, Affiliated Hospital of Medical College Qingdao University, Qingdao, China

关键词: Docetaxel resistance;    Prognosis;    Gastric cancer;    FOXM1;   

Others  :  826722
DOI  :  10.1186/1479-5876-11-204

 received in 2013-06-19, accepted in 2013-09-02,  发布年份 2013

【 摘 要 】

Background

Forkhead 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.

Methods

We 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.

Results

Our 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.

Conclusions

FOXM1 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.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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