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Nrf2 Signaling Pathway: A Comprehensive Prognostic and Gene Expression Profile Analysis in Breast Cancer Publisher Pubmed



Soghli N1 ; Yousefi H2, 3 ; Naderi T4 ; Fallah A5 ; Moshksar A6 ; Darbeheshti F7 ; Vittori C3 ; Delavar MR8 ; Zare A9 ; Rad HS10 ; Kazemi A11 ; Bitaraf A12 ; Hussen BM13 ; Taheri M14, 15 Show All Authors
Authors
  1. Soghli N1
  2. Yousefi H2, 3
  3. Naderi T4
  4. Fallah A5
  5. Moshksar A6
  6. Darbeheshti F7
  7. Vittori C3
  8. Delavar MR8
  9. Zare A9
  10. Rad HS10
  11. Kazemi A11
  12. Bitaraf A12
  13. Hussen BM13
  14. Taheri M14, 15
  15. Jamali E16

Source: Pathology Research and Practice Published:2023


Abstract

Breast cancer is the most frequently diagnosed malignant tumor in women and a major public health concern. NRF2 axis is a cellular protector signaling pathway protecting both normal and cancer cells from oxidative damage. NRF2 is a transcription factor that binds to the gene promoters containing antioxidant response element-like sequences. In this report, differential expression of NRF2 signaling pathway elements, as well as the correlation of NRF2 pathway mRNAs with various clinicopathologic characteristics, including molecular subtypes, tumor grade, tumor stage, and methylation status, has been investigated in breast cancer using METABRIC and TCGA datasets. In the current report, our findings revealed the deregulation of several NRF2 signaling elements in breast cancer patients. Moreover, there were negative correlations between the methylation of NRF2 genes and mRNA expression. The expression of NRF2 genes significantly varied between different breast cancer subtypes. In conclusion, substantial deregulation of NRF2 signaling components suggests an important role of these genes in breast cancer. Because of the clear associations between mRNA expression and methylation status, DNA methylation could be one of the mechanisms that regulate the NRF2 pathway in breast cancer. Differential expression of Hippo genes among various breast cancer molecular subtypes suggests that NRF2 signaling may function differently in different subtypes of breast cancer. Our data also highlights an interesting link between NRF2 components' transcription and tumor grade/stage in breast cancer. © 2023 Elsevier GmbH
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