Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer
| Autor: | Xiu-Feng Hu, Yan-Tong Yang, Jun Yao, Xinshuai Wang, Xiaoshan Feng, She-Gan Gao, Xiu-Qing Peng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Antimetabolites Antineoplastic Epidemiology NF-E2-Related Factor 2 medicine.medical_treatment Drug resistance Biology Adenocarcinoma digestive system environment and public health In vivo Gastrectomy Stomach Neoplasms Cell Line Tumor medicine Biomarkers Tumor Gene silencing Humans Viability assay Aged Proportional Hazards Models Chemotherapy Public Health Environmental and Occupational Health Cancer Combination chemotherapy respiratory system medicine.disease Prognosis Immunohistochemistry Gene Expression Regulation Neoplastic Oncology Drug Resistance Neoplasm Multivariate Analysis Cancer research Female Fluorouracil |
| Zdroj: | Asian Pacific journal of cancer prevention : APJCP. 14(9) |
| ISSN: | 2476-762X |
| Popis: | Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC. |
| Databáze: | OpenAIRE |
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