Nrf2 Overexpression Predicts Prognosis and 5-FU Resistance in Gastric Cancer
Nrf2 Overexpression Predicts Prognosis and 5-FU Resistance in Gastric Cancer
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DOI：
10.7314/apjcp.2013.14.9.5231
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Feng, Xiao-Shan
中科院分区：
文献类型：
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作者：
Hu, Xiu-Feng;Yao, Jun;Feng, Xiao-Shan
目的：NF-E2相关因子2（Nrf 2）在几种人类恶性肿瘤中被激活。然而，Nrf 2在胃癌（GC）中的作用仍不完全清楚。因此，在这项研究中，我们分析了Nrf 2表达状态与胃癌临床特征和化疗耐药性的关系。材料和方法：对186例胃癌患者行胃切除术后的胃粘膜进行预后评估。另外142例接受一线联合化疗的胃癌患者的样本用于耐药性调查。采用免疫组化法检测胃癌组织中Nrf 2的表达，分析其与临床病理参数及化疗敏感性的关系。通过体内细胞存活率测定来检查Nrf 2基因沉默对化疗抗性的影响。结果：186例胃癌中，104例（55.9%）Nrf 2高表达。Nrf 2的过表达是总生存期[ OS，风险比（HR）3.9; P=0.011]和无病生存期（DFS，HR 4.3; P=0.002）的独立预测因子。Nrf 2基因沉默降低了GC细胞系对5-FU诱导的细胞死亡的抵抗力。结论：Nrf 2是胃癌的独立预后因子。此外，Nrf 2在GC细胞中赋予对化疗药物5-FU的抗性。总之，Nrf 2是一个潜在的预后标志物和预测5-FU耐药的GC。
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.