High NF-E2-related factor 2 expression predicts poor prognosis in patients with lung cancer: a meta-analysis of cohort studies

Abstract

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 p=.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 p=.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.

Keywords:

• Chemotherapy
• lung cancer
• meta-analysis
• Nrf2
• prognosis

Declarations

Ethics approval and consent to participate

The included studies have been approved by local ethics committees.

Consent for publication

Informed consent has been obtained from all participants.

Availability of data and material

All data supporting the findings of this study are available within the article and its supplementary information files.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Chinese National Natural Science Foundation (81811540034; 81573173; 81872646), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).