High Expression of NRF2 and Low Expression of KEAP1 Predict Worse Survival in Patients With Operable Triple-Negative Breast Cancer
Young Sub Lee, Jun Kang, Eun Sun Jung, Ahwon Lee
Abstract
PURPOSE: ) gene and its endogenous inhibitor, Kelch-like ECH-associated protein 1 (KEAP1), both participate in cellular defense mechanisms against oxidative stress and contribute to chemoresistance and tumor progression in numerous types of cancers. This study aimed to evaluate the expression patterns of NRF2 and KEAP1 and their prognostic value in operable TNBC. METHODS: Tissue microarrays were prepared using tumor tissues collected from 203 patients with TNBC who underwent surgery. Immunohistochemical staining analyses of NRF2 and KEAP1 were performed. The expression of each immunomarker was categorized into two groups (low or high) based on the median H-score. We analyzed the association between the expression of each immunomarker and clinicopathological information to predict survival. A total of 225 TNBC samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate our results. RESULTS: = 0.009) in the METABRIC dataset. CONCLUSION: High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.