title: Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, Cancer Research Institute, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China E-mail : xiaoshan_feng@126.com.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: She-Gan
authors.initials: SG
authors.lastname: Gao
authors.forename: Xin-Shuai
authors.initials: XS
authors.lastname: Wang
authors.forename: Xiu-Qing
authors.initials: XQ
authors.lastname: Peng
authors.forename: Yan-Tong
authors.initials: YT
authors.lastname: Yang
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Feng
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D005472:Fluorouracil