Correlation of Nrf2 and HIF-1α in glioblastoma and their relationships to clinicopathologic features and survival

Abstract

ObjectivesGlioblastoma (GB) is the most common, aggressive, and proliferative among all brain tumors. The prognosis of GB is still far from satisfactory currently, thus demanding great modification and enhancement, which may be acquired by the help of the molecular target therapy. Nuclear factor E2-related factor 2 (Nrf2), a pivotal transcriptional factor of cellular responses to oxidative stress, was observed to function remarkably in cancer pathobiology. In the current study, we analyzed the correlation between Nrf2 and Hypoxia-inducible factor-1alpha (HIF-1alpha) in GB, together with their association to the features and survival of clinicopathology.Methods:We examined the expression of Nrf2 and HIF-1alpha in 68 specimens of GB by tissue microarray and immunohistochemistry, and correlated this investigation to the outcome of GB patients.Results:Nrf2 and HIF-1alpha were overexpressed in GB tissues. There was significant correlation between the high level of Nrf2 and tumor necrosis on MRI and 1-year survival. There was significant correlation between HIF-1alpha level and Nrf2 status (r = 0·294, P = 0·015). Kaplan–Meier analysis showed that high Nrf2 expression was significantly associated with shorter overall survival (OS) (log-rank test, P = 0·006), and was identified as an independent prognostic factor in multivariate analysis (P = 0·034). HIF-1alpha was another independent factor for both OS and progression-free survival by Cox regression analysis (P = 0·048 and P = 0·032, respectively).Discussion:Mutual association between Nrf2 and HIF-1alpha was found in GB: higher Nrf2 expression and poorer outcome of GB patients. Nrf2 would therefore be a new molecular marker for the targeted treatment of GB.