title: Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel.
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.
authors.affiliation: Department of Oncology, Affiliated Hospital of Medical College Qingdao University, 16 Jiangsu Road, Qingdao 266003, China. ljqyfy@163.com.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.forename: Wensheng
authors.initials: W
authors.lastname: Qiu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Ruyong
authors.initials: R
authors.lastname: Yao
authors.forename: Shihai
authors.initials: S
authors.lastname: Liu
authors.forename: Yasai
authors.initials: Y
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010641:Phenotype; D011182:Postoperative Care; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D013883:Thiostrepton / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D013883:Thiostrepton