NRF2 immunolocalization in human breast cancer patients as a prognostic factor

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important transcriptional activator involved in the cellular defense mechanisms against electrophilic and oxidative stress. Recent studies have demonstrated that the expression of NRF2 protein is upregulated in several human malignancies and is associated with worse prognosis in these patients. However, the pathological and clinical significance of NRF2 has remained largely unknown in breast cancer patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was significantly associated with histological grade, Ki-67 labeling index, p62 immunoreactivity, and NAD(P) H:quinone oxidoreductase 1 (NQO1) immunoreactivity, and the results of multivariate analyses revealed that NRF2 status was an independent adverse prognostic factor for both recurrence and disease-free survival of the patients. Subsequent in vitro studies demonstrated that the expression of NRF2 significantly increased the proliferation activity of MCF7 and SK-BR-3 breast carcinoma cells. These results indicate that nuclear NRF2 protein plays important roles in the proliferation and/or progression of breast carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor in breast cancer patients.

Impact of nuclear factor erythroid-derived 2–like 2 and p62/sequestosome expression on prognosis of patients with gliomas

“…Glioma patients with high Nrf2 expression had significantly shorter OS and DFS than glioma patients with low Nrf2 expression. Our results are consistent with the results reported in previous studies, in which high Nrf2 expression indicated the poor outcomes in malignant tumors [8][9][10]. In addition, high Nrf2 expression correlates with high tumor grade and indicates high degree of malignancy in gliomas.…”

“…However, the protective effects of Nrf2 cannot discriminate the normal cells from cancer cells [7]. It has been demonstrated that high levels of Nrf2 promote cancer cell survival; contribute to chemoresistance; and associate with poor prognosis in a variety of malignant tumors, such as lung cancer, pancreatic cancer, and breast cancer [8][9][10].…”

Mutations and expression of the NFE2L2/KEAP1/CUL3 pathway in Chinese patients with lung squamous cell carcinoma

“…A number of studies have reported the abnormal incidence of mutations in the NFE2L2/KEAP1/CUL3 pathway and high expression of NFE2L2 in various cancers, in agreement with our results (9,(18)(19)(20)(21). Nevertheless, there are some controversial views about the expression of KEAP1 in tumorigenesis.…”

TACC2 (transforming acidic coiled‐coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation

“…Briefly, the confluent cell layer was scratched using a sterile plastic P‐200 pipette tip after transfection and incubated for 48  h. The migration area was evaluated using the MultiGauge v3.1 Software (Fuji Photo Film, Tokyo, Japan), and the relative migration area was then calculated as the ratio of that in the control cells transfected with negative control (NC) in this study 16.…”