Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis.
Keap1
Nrf2
Radiation Therapy
Rectal Cancer
Tumor Regression
Journal
Journal of Korean medical science
ISSN: 1598-6357
Titre abrégé: J Korean Med Sci
Pays: Korea (South)
ID NLM: 8703518
Informations de publication
Date de publication:
03 Jul 2023
03 Jul 2023
Historique:
received:
17
09
2022
accepted:
16
04
2023
medline:
5
7
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
epublish
Résumé
The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.
Sections du résumé
BACKGROUND
BACKGROUND
The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC).
METHODS
METHODS
In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed.
RESULTS
RESULTS
The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity.
CONCLUSION
CONCLUSIONS
CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.
Identifiants
pubmed: 37401495
pii: 38.e200
doi: 10.3346/jkms.2023.38.e200
pmc: PMC10318200
doi:
Substances chimiques
Kelch-Like ECH-Associated Protein 1
0
NF-E2-Related Factor 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e200Subventions
Organisme : National Research Foundation of Korea
ID : 2021R1F1A1064310
Pays : Korea
Organisme : National Research Foundation of Korea
ID : 2021M3E5D7102565
Pays : Korea
Organisme : National Research Foundation of Korea
ID : 2018R1C1B5085744
Pays : Korea
Organisme : National Research Foundation of Korea
ID : 2022R1C1C1012908
Pays : Korea
Informations de copyright
© 2023 The Korean Academy of Medical Sciences.
Déclaration de conflit d'intérêts
The authors have no potential conflicts of interest to disclose.
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