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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 (author)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Central Hospital Kristianstad
De Marchi, Tommaso (author)
Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Pekar, Gyula (author)
Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,Breast cancer Proteogenomics,Lund University Research Groups
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Tran, Lena (author)
Lund University,Lunds universitet,Bröst- och ovarialcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/ovarialcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breast and Ovarian Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/ovarian cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Bendahl, Pär Ola (author)
Lund University,Lunds universitet,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröstcancerbehandling,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Personalized Breast Cancer Treatment,Lund University Research Groups,The Liquid Biopsy and Tumor Progression in Breast Cancer,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast cancer treatment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Stenmark Tullberg, Axel (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
Holmberg, Erik, 1951 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
Karlsson, Per, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
Farnebo, Marianne (author)
Karolinska Institutet,Karolinska Institute
Killander, Fredrika (author)
Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröstcancerbehandling,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast cancer treatment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Nimeús, Emma (author)
Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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 (creator_code:org_t)
2023-03-28
2023
English.
In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:10, s. 2029-2040
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

breast cancer
DNA repair
prediction
prognosis
radiotherapy
WRAP53

Publication and Content Type

art (subject category)
ref (subject category)

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