Tong Ying-Hui, Zhang Bo, Yan You-You, Fan Yun, Yu Jia-Wen, Kong Si-Si, Zhang Dan, Fang Luo, Su Dan, Lin Neng-Ming
Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
Laboratory of Clinical Pharmacology, Translational Medicine Research Center, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, China.
Oncotarget. 2017 Jul 11;8(28):45750-45758. doi: 10.18632/oncotarget.17403.
Functional studies in non-small cell lung cancer (NSCLC) patients revealed that hyperactivation of the NF-E2-related factor 2 (Nrf2) pathway facilitates tumor growth. We examined the usefulness of Nrf2 and NQO1 as indicators of prognosis in NSCLC. Tumor and adjacent non-tumor tissue samples were collected from 215 NSCLC patients who had tumor resections between 2006 and 2011. Immunohistochemistry was performed to detect Nrf2 or NQO1 expression. The correlation between Nrf2 or NQO1 expression and survival outcomes was evaluated using the Kaplan-Meier method and Cox proportional hazards regression model. Levels of Nrf2 and NQO1 were elevated in tumor tissues. In particular, Nrf2 was elevated in nearly all tumor cells. NQO1 expression positively correlated with Nrf2 expression (P = 0.039). Nrf2 expression positively correlated with lymph node metastasis (P = 0.001) and negatively correlated with tumor differentiation (P = 0.032). As compared with either Nrf2 or NQO1 alone, dual-negative expression of Nrf2 and NQO1 was more predictive of superior overall survival (P = 0.020) and disease free survival (P = 0.037). Subgroup analyses showed that females, nonsmokers, and patients with advanced-stage NSCLC were suitable populations in which to evaluate prognosis based on Nrf2 and NQO1 co-expression. These results indicate that dual-negative expression of Nrf2 and NQO1 is predictive of a better prognosis in NSCLC patients.
对非小细胞肺癌（NSCLC）患者的功能研究表明，核因子E2相关因子2（Nrf2）通路的过度激活促进肿瘤生长。我们研究了Nrf2和NQO1作为NSCLC预后指标的实用性。收集了2006年至2011年间接受肿瘤切除术的215例NSCLC患者的肿瘤及相邻非肿瘤组织样本。采用免疫组织化学法检测Nrf2或NQO1的表达。使用Kaplan-Meier法和Cox比例风险回归模型评估Nrf2或NQO1表达与生存结果之间的相关性。肿瘤组织中Nrf2和NQO1的水平升高。特别是，几乎所有肿瘤细胞中的Nrf2都升高。NQO1表达与Nrf2表达呈正相关（P = 0.039）。Nrf2表达与淋巴结转移呈正相关（P = 0.001），与肿瘤分化呈负相关（P = 0.032）。与单独的Nrf2或NQO1相比，Nrf2和NQO1的双阴性表达更能预测较好的总生存期（P = 0.020）和无病生存期（P = 0.037）。亚组分析表明，女性、不吸烟者和晚期NSCLC患者是基于Nrf2和NQO1共表达评估预后的合适人群。这些结果表明，Nrf2和NQO1的双阴性表达可预测NSCLC患者的预后较好。
