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Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer : a long-term follow-up of the SweBCG91RT randomized trial

Egelberg, Moa LU orcid ; De Marchi, Tommaso LU ; Pekar, Gyula LU ; Tran, Lena LU ; Bendahl, Pär Ola LU ; Tullberg, Axel Stenmark ; Holmberg, Erik ; Karlsson, Per ; Farnebo, Marianne and Killander, Fredrika LU , et al. (2023) In Molecular Oncology 17(10). p.2029-2040
Abstract

Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively. Correlation with local recurrence and breast cancer-related death was assessed for prognosis, and the interaction between WRAP53 and radiotherapy in relation to local recurrence was assessed for radioresistance prediction. Tumors... (More)

Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively. Correlation with local recurrence and breast cancer-related death was assessed for prognosis, and the interaction between WRAP53 and radiotherapy in relation to local recurrence was assessed for radioresistance prediction. Tumors with low WRAP53 protein levels had a higher subhazard ratio (SHR) for local recurrence [1.76 (95% CI 1.10–2.79)] and breast cancer-related death [1.55 (1.02–2.38)]. Low WRAP53 RNA levels were associated with almost a three-fold decreased effect of radiotherapy in relation to ipsilateral breast tumor recurrence [IBTR; SHR 0.87 (95% CI 0.44–1.72)] compared with high RNA levels [0.33 (0.19–0.55)], with a significant interaction (P = 0.024). In conclusion, low WRAP53 protein is prognostic for local recurrence and breast cancer-related death. Low WRAP53 RNA is a potential marker for radioresistance.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, DNA repair, prediction, prognosis, radiotherapy, WRAP53
in
Molecular Oncology
volume
17
issue
10
pages
2029 - 2040
publisher
Elsevier
external identifiers
  • pmid:36975842
  • scopus:85153371726
ISSN
1574-7891
DOI
10.1002/1878-0261.13426
language
English
LU publication?
yes
id
6b0a25ba-9061-4415-92e7-75aa3b935bd4
date added to LUP
2023-07-17 12:08:22
date last changed
2024-04-19 23:35:06
@article{6b0a25ba-9061-4415-92e7-75aa3b935bd4,
  abstract     = {{<p>Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively. Correlation with local recurrence and breast cancer-related death was assessed for prognosis, and the interaction between WRAP53 and radiotherapy in relation to local recurrence was assessed for radioresistance prediction. Tumors with low WRAP53 protein levels had a higher subhazard ratio (SHR) for local recurrence [1.76 (95% CI 1.10–2.79)] and breast cancer-related death [1.55 (1.02–2.38)]. Low WRAP53 RNA levels were associated with almost a three-fold decreased effect of radiotherapy in relation to ipsilateral breast tumor recurrence [IBTR; SHR 0.87 (95% CI 0.44–1.72)] compared with high RNA levels [0.33 (0.19–0.55)], with a significant interaction (P = 0.024). In conclusion, low WRAP53 protein is prognostic for local recurrence and breast cancer-related death. Low WRAP53 RNA is a potential marker for radioresistance.</p>}},
  author       = {{Egelberg, Moa and De Marchi, Tommaso and Pekar, Gyula and Tran, Lena and Bendahl, Pär Ola and Tullberg, Axel Stenmark and Holmberg, Erik and Karlsson, Per and Farnebo, Marianne and Killander, Fredrika and Nimeús, Emma}},
  issn         = {{1574-7891}},
  keywords     = {{breast cancer; DNA repair; prediction; prognosis; radiotherapy; WRAP53}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2029--2040}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Oncology}},
  title        = {{Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer : a long-term follow-up of the SweBCG91RT randomized trial}},
  url          = {{http://dx.doi.org/10.1002/1878-0261.13426}},
  doi          = {{10.1002/1878-0261.13426}},
  volume       = {{17}},
  year         = {{2023}},
}