Loss of Beclin1 Expression and Nrf2 Overexpression are Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer

Abstract

Background: Nrf2 pathway and autophagy are abnormally activated in response to cellular stress in various types of human cancers. In this study, we selected Beclin1 as an enter point to discuss the relationship between Nrf2 pathway and autophagy, and defined their associations with clinic pathological features and survival of the patients. Method: NSCLC specimens were processed for immunohistochemical and qRT-PCR to analyses the expression of Beclin1 and Nrf2. Kaplan-Meier method and log-rank test were used in the survival data. Results: Beclin1 protein level was found to be significantly associated with more advanced TNM stage (P = 0.035), lymph node metastasis (P = 0.017) and distant metastasis (P = 0.005). The expression of Nrf2 protein was associated with larger tumor size (P = 0.032), more advanced TNM stage (P = 0.011), lymph node metastasis (P = 0.045) and distant metastasis (P = 0.013). Beside there was a strong inverse relationship between Beclin1 and Nrf2 expression in the NSCLC tissues. Distant metastasis, Beclin1, Nrf2, and Beclin1-/Nrf2+ expression was conformed to be independent prognostic factors of patients. Conclusion: Both Nrf2 overexpression and Beclin1 lower-expression are independent indicators of a poor prognosis in NSCLC patients.