Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel
| Autor: | Wensheng Qiu, Jun Liang, Shihai Liu, Bin Liu, Yasai Yao, Ruyong Yao, Xiaoxiao Li |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Down-Regulation Apoptosis Drug resistance Docetaxel Kaplan-Meier Estimate Biology Microtubules General Biochemistry Genetics and Molecular Biology Stomach Neoplasms Cell Line Tumor medicine Humans Clinical significance RNA Messenger Neoplasm Staging Medicine(all) Postoperative Care Biochemistry Genetics and Molecular Biology(all) Research Forkhead Box Protein M1 FOXM1 Cancer Forkhead Transcription Factors General Medicine Middle Aged medicine.disease Prognosis Thiostrepton Up-Regulation Gene Expression Regulation Neoplastic Phenotype Drug Resistance Neoplasm Cancer cell Multivariate Analysis Docetaxel resistance Cancer research Immunohistochemistry Female Taxoids FOXA1 Gastric cancer medicine.drug |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | 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 0.1). 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. |
| Databáze: | OpenAIRE |
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