Yang Qianlei, Deng Hanyi, Xia Haixuan, Xu Mengchuan, Pan Guotao, Mao Jiayuan, Tao Shasha, Yamanaka Kenzo, An Yan
Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Shanghai Municipal Center for Disease Control & Prevention, Shanghai, China.
Free Radic Res. 2020 Dec;54(11-12):790-798. doi: 10.1080/10715762.2019.1642472. Epub 2019 Jul 24.
NF-E2-related factor 2 (Nrf2) plays an important role in tumour proliferation and chemoresistance. Nrf2 expression levels may be associated with prognosis of lung cancer, but previous results have been inconsistent. Pooled hazard ratios (HRs) and odds ratios were calculated to assess the prognostic value of the Nrf2 expression in this meta-analysis. Nine studies with 940 patients were included. A high Nrf2 expression level was significantly related to decreased overall survival (OS) (HR = 1.948, 95% CI = 1.564-2.427), lower response rate (HR = 2.675, 95% CI = 1.553-4.610), and poor progression-free survival (HR = 3.078, 95% CI = 1.791-5.293). Subgroup analysis demonstrated that high-Nrf2-expression was significantly correlated with worse OS of patients possessing epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or undergoing chemotherapeutic treatments (HR = 2.500, 95% CI = 1.556-4.018). Conversely, this high expression was not significantly related to the OS of patients with surgical resection (HR = 1.750, 95% CI = 0.995-3.080, and =.052). High Nrf2 expression was significantly correlated with worse OS of patients in advanced stage (HR = 2.500, 95% CI = 1.556-4.018), compared with early cancer stage (HR = 1.609, 95% CI = 0.675-3.835, and =.283). This meta-analysis suggests that high Nrf2 expression may be a predictive factor of poor outcomes in lung cancer. Therefore, Nrf2 likely plays an important role in prognostic evaluation and may be a therapeutic target for EGFR-TKIs therapy and chemotherapy.
核因子E2相关因子2(Nrf2)在肿瘤增殖和化疗耐药中起重要作用。Nrf2表达水平可能与肺癌预后相关,但先前的结果并不一致。在这项荟萃分析中,计算合并风险比(HRs)和优势比以评估Nrf2表达的预后价值。纳入了9项研究,共940例患者。Nrf2高表达水平与总生存期(OS)降低显著相关(HR = 1.948,95%CI = 1.564 - 2.427)、缓解率降低(HR = 2.675,95%CI = 1.553 - 4.610)以及无进展生存期较差(HR = 3.078,95%CI = 1.791 - 5.293)。亚组分析表明,Nrf2高表达与接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR - TKIs)治疗或化疗的患者较差的OS显著相关(HR = 2.500,95%CI = 1.556 - 4.018)。相反,这种高表达与手术切除患者的OS无显著相关性(HR = 1.750,95%CI = 0.995 - 3.080,P = 0.052)。与早期癌症阶段相比,Nrf2高表达与晚期患者较差的OS显著相关(HR = 2.500,95%CI = 1.556 - 4.018),而早期癌症阶段的HR = 1.609,95%CI = 0.675 - 3.835,P = 0.283。这项荟萃分析表明,Nrf2高表达可能是肺癌预后不良的预测因素。因此,Nrf2可能在预后评估中起重要作用,并且可能是EGFR - TKIs治疗和化疗的治疗靶点。