New insights into the mechanism of Keap1-Nrf2 interaction based on cancer-associated mutations

Cheng, Liangkai; Li, Shehan; Liu, Zhongqiu; Wang, Caiyan

doi:10.1016/j.lfs.2021.119791

Cited by 3 publications

(1 citation statement)

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“…There was a study that reported that NRF2/KEAP1 mutations correlate with higher TMB value/PD-L1 expression and potentiate improved clinical outcomes with immunotherapy [ 45 ]. An NRF2 mutation could disrupt the weak binding of Keap1 with the NRF2-DLG motif and activate NRF2 to promote tumor progression [ 46 ]. Considering the complexity of mutations, we only detected the expression of NRF2 and the prognosis value in EC.…”

Section: Discussionmentioning

confidence: 99%

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

Guo

Shen

Sun

et al. 2023

Journal of Oncology

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Background. Esophageal cancer (EC) had the sixth-highest mortality rate of all cancers due to its poor prognosis. Immune cells and mutation genes influenced the prognosis of EC, but their combined effect on predicting EC prognosis was unknown. In this study, we comprehensively analyzed the immune cell infiltration (ICI) and mutation genes and their combined effects for predicting prognosis in EC. Methods. The CIBERSORT and ESTIMATE algorithms were used to analyse the ICI scape based on the TCGA and GEO databases. EC tissues and pathologic sections from Huai’an, China, were used to verify the key immune cells and mutation genes and their interactions. Results. Stromal/immune score patterns and ICI/gene had no statistical significance in overall survival (OS) ( p > 0.05 ). The combination of ICI and tumor mutation burden (TMB) showed that the high TMB and high ICI score group had the shortest OS ( p = 0.004 ). We recognized that the key mutation gene NRF2 was significantly different in the high/low ICI score subgroups ( p = 0.002 ) and positivity with mast cells (MCs) ( p < 0.05 ). Through experimental validation, we found that the MCs and activated mast cells (AC-MCs) were more infiltration in stage II/III ( p = 0.032 ; p = 0.013 ) of EC patients and that NRF2 expression was upregulated in EC ( p = 0.045 ). AC-MCs combined with NRF2 had a poor prognosis, according to survival analysis ( p = 0.056 ) and interactive analysis ( p = 0.032 ). Conclusions. We presume that NRF2 combined with AC-MCs could be a marker to predict prognosis and could influence immunotherapy through regulating PD-L1 in the EC.

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Section: Discussionmentioning

confidence: 99%