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Autoimmunity to selenoprotein P predicts breast cancer recurrence

BACKGROUND: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subje...

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Autores principales: Demircan, Kamil, Sun, Qian, Bengtsson, Ylva, Seemann, Petra, Vallon-Christersson, Johan, Malmberg, Martin, Saal, Lao H., Rydén, Lisa, Minich, Waldemar B., Borg, Åke, Manjer, Jonas, Schomburg, Lutz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157254/
https://www.ncbi.nlm.nih.gov/pubmed/35636018
http://dx.doi.org/10.1016/j.redox.2022.102346
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author Demircan, Kamil
Sun, Qian
Bengtsson, Ylva
Seemann, Petra
Vallon-Christersson, Johan
Malmberg, Martin
Saal, Lao H.
Rydén, Lisa
Minich, Waldemar B.
Borg, Åke
Manjer, Jonas
Schomburg, Lutz
author_facet Demircan, Kamil
Sun, Qian
Bengtsson, Ylva
Seemann, Petra
Vallon-Christersson, Johan
Malmberg, Martin
Saal, Lao H.
Rydén, Lisa
Minich, Waldemar B.
Borg, Åke
Manjer, Jonas
Schomburg, Lutz
author_sort Demircan, Kamil
collection PubMed
description BACKGROUND: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subjects, and in patients with thyroid disease. Given the potential transport disrupting properties, we hypothesized that breast cancer patients with SELENOP-aAb may have a poor prognosis. METHODS: SELENOP-aAb along with serum Se, SELENOP and GPX3 activity were determined in serum samples of 1988 patients with a new diagnosis of breast cancer enrolled in the multicentre SCAN-B study. Patients were followed for ∼9 years and multivariate Cox regression models were applied to assess hazard ratios. RESULTS: Applying a cut-off based on outlier detection, we identified 7.65% of patients with SELENOP-aAb. Autoantibody titres correlated positively to total Se and SELENOP concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but independent of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI) = 1.87(1.17–2.99), particularly in patients with low Se concentrations, HR(95%CI) = 2.16(1.20–3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1.25(1.01–1.55) and 1.31(1.13–1.51), respectively. CONCLUSION: Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast cancer, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, independent of established prognostic factors, who may respond favourably to Se supplementation.
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spelling pubmed-91572542022-06-02 Autoimmunity to selenoprotein P predicts breast cancer recurrence Demircan, Kamil Sun, Qian Bengtsson, Ylva Seemann, Petra Vallon-Christersson, Johan Malmberg, Martin Saal, Lao H. Rydén, Lisa Minich, Waldemar B. Borg, Åke Manjer, Jonas Schomburg, Lutz Redox Biol Research Paper BACKGROUND: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subjects, and in patients with thyroid disease. Given the potential transport disrupting properties, we hypothesized that breast cancer patients with SELENOP-aAb may have a poor prognosis. METHODS: SELENOP-aAb along with serum Se, SELENOP and GPX3 activity were determined in serum samples of 1988 patients with a new diagnosis of breast cancer enrolled in the multicentre SCAN-B study. Patients were followed for ∼9 years and multivariate Cox regression models were applied to assess hazard ratios. RESULTS: Applying a cut-off based on outlier detection, we identified 7.65% of patients with SELENOP-aAb. Autoantibody titres correlated positively to total Se and SELENOP concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but independent of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI) = 1.87(1.17–2.99), particularly in patients with low Se concentrations, HR(95%CI) = 2.16(1.20–3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1.25(1.01–1.55) and 1.31(1.13–1.51), respectively. CONCLUSION: Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast cancer, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, independent of established prognostic factors, who may respond favourably to Se supplementation. Elsevier 2022-05-25 /pmc/articles/PMC9157254/ /pubmed/35636018 http://dx.doi.org/10.1016/j.redox.2022.102346 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Demircan, Kamil
Sun, Qian
Bengtsson, Ylva
Seemann, Petra
Vallon-Christersson, Johan
Malmberg, Martin
Saal, Lao H.
Rydén, Lisa
Minich, Waldemar B.
Borg, Åke
Manjer, Jonas
Schomburg, Lutz
Autoimmunity to selenoprotein P predicts breast cancer recurrence
title Autoimmunity to selenoprotein P predicts breast cancer recurrence
title_full Autoimmunity to selenoprotein P predicts breast cancer recurrence
title_fullStr Autoimmunity to selenoprotein P predicts breast cancer recurrence
title_full_unstemmed Autoimmunity to selenoprotein P predicts breast cancer recurrence
title_short Autoimmunity to selenoprotein P predicts breast cancer recurrence
title_sort autoimmunity to selenoprotein p predicts breast cancer recurrence
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157254/
https://www.ncbi.nlm.nih.gov/pubmed/35636018
http://dx.doi.org/10.1016/j.redox.2022.102346
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