Expression of thioredoxin system and related peroxiredoxin proteins is associated with clinical outcome in radiotherapy treated early stage breast cancer

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

Abstract

Background and purpose
Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Expression of the thioredoxin system proteins (thioredoxin, thioredoxin reductase and thioredoxin interacting protein) and downstream peroxiredoxins (I–VI), was examined in tumor specimens from early stage breast cancer patients, subsequently treated by breast conserving surgery and locoregional radiotherapy, to determine if redox protein expression is associated with clinical outcome.

Material and methods
Nuclear and cytoplasmic expression was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors.

Results
High expression of cytoplasmic peroxiredoxin-I correlated with a greater risk of local recurrence ( p = 0.009). When nuclear and cytoplasmic expression patterns were combined, patients with low nuclear but high cytoplasmic expression of peroxiredoxin-I increased significance ( p = 0.005). Both were independent factors ( p = 0.006 and 0.003) from multivariate analysis. Associations were obtained between tumor grade and nuclear thioredoxin interacting protein ( p = 0.01) and with cytoplasmic expression of peroxiredoxin-V ( p = 0.007) but not with peroxiredoxin-I suggesting that the latter may exert influence via regulation of oxidative stress rather than via altering the tumor phenotype.

Conclusions
Results highlight the potential of using redox protein expression, namely peroxiredoxin-I, to predict clinical outcome and support further studies to validate its usefulness as an independent prognostic, and potentially predictive, marker.

• Journal Article Type: Article
• Acceptance Date: May 12, 2011
• Online Publication Date: Jun 6, 2011
• Publication Date: 2011-08
• Deposit Date: Oct 12, 2020
• Journal: Radiotherapy and Oncology
• Print ISSN: 0167-8140
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 100
• Issue: 2
• Pages: 308-313
• DOI: https://doi.org/10.1016/j.radonc.2011.05.029
• Keywords: Oncology; Radiology Nuclear Medicine and imaging; Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/4958922
• Publisher URL: https://www.thegreenjournal.com/article/S0167-8140(11)00222-2/fulltext
• Related Public URLs: https://www.sciencedirect.com/science/article/abs/pii/S0167814011002222