Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resista
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RESEARCH
Open Access
Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel Xiaoxiao Li1†, Wensheng Qiu1†, Bin Liu2, Ruyong Yao3, Shihai Liu3, Yasai Yao1 and Jun Liang1*
Abstract 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. Keywords: FOXM1, Gastric cancer, Prognosis, Docetaxel resistance
Background Despite the developments of surgical technique and improvements of anticancer drugs recently, gastric cancer is still the main cause of death and strongly associated with poor outcome. So far, in China, the morbidity of gastric cancer has reached to second with 3,621,000 new cases, whilst the mortality rate ranked third with the proportion of 14.33% each year [1]. 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 * Correspondence: [email protected] † Equal contributors 1 Department of Oncology, Affiliated Hospital of Medical College Qingdao University, 16 Jiangsu Road, Qingdao 266003, China Full list of author information is available at the end of the article
choice of treatment. Among new generation chemotherapy regimens, docetaxel, which is a semisynthetic taxane, promoting the assembly and stabilization of microtubules to inhibit the depolymerization [3], has been used more and more extensively with potent effe
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