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Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

Woolston, Caroline M.; Al-Attar, Ahmad; Ellis, Ian O.; Storr, Sarah J.; Morgan, David A.L.; Martin, Stewart G.

Authors

Caroline M. Woolston

Ahmad Al-Attar

Ian O. Ellis

Profile image of SARAH STORR

SARAH STORR sarah.storr@nottingham.ac.uk
Assistant Professor

David A.L. Morgan

STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology



Abstract

Purpose

Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response.

Methods and Materials

The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-θ, -π, and -α) was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors.

Results

A high cytoplasmic expression of glutathione S-transferase-θ significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-θ also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade.

Conclusions

Our results support the use of redox protein expression, namely glutathione S-transferase-θ and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated into routine diagnostic tests, they have the potential to aid clinicians in their stratification of patients into more tailored treatment regimens. Future targeted therapies to these systems might improve the efficacy of reactive oxygen species-inducing therapies, such as radiotherapy.

Citation

Woolston, C. M., Al-Attar, A., Ellis, I. O., Storr, S. J., Morgan, D. A., & Martin, S. G. (2011). Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients. International Journal of Radiation Oncology - Biology - Physics, 79(5), 1532-1540. https://doi.org/10.1016/j.ijrobp.2010.11.002

Journal Article Type Article
Acceptance Date Nov 2, 2010
Online Publication Date Feb 7, 2011
Publication Date 2011-04
Deposit Date Oct 12, 2020
Journal International Journal of Radiation Oncology*Biology*Physics
Print ISSN 0360-3016
Electronic ISSN 1879-355X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 79
Issue 5
Pages 1532-1540
DOI https://doi.org/10.1016/j.ijrobp.2010.11.002
Keywords Cancer Research; Oncology; Radiation; Radiology Nuclear Medicine and imaging
Public URL https://nottingham-repository.worktribe.com/output/4958885
Publisher URL https://www.redjournal.org/article/S0360-3016(10)03486-3/fulltext
Related Public URLs https://www.sciencedirect.com/science/article/pii/S0360301610034863