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Autoimmunity to selenoprotein P predicts breast cancer recurrence

Demircan, Kamil ; Sun, Qian ; Bengtsson, Ylva LU orcid ; Seemann, Petra ; Vallon-Christersson, Johan LU orcid ; Malmberg, Martin ; Saal, Lao LU orcid ; Ryden, Lisa LU orcid ; Minich, Waldemar B. and Borg, Åke LU , et al. (2022) In Redox Biology 53.
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Redox Biology
volume
53
article number
102346
publisher
Elsevier
external identifiers
  • scopus:85130779035
  • pmid:35636018
ISSN
2213-2317
DOI
10.1016/j.redox.2022.102346
project
Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
language
English
LU publication?
yes
id
363e19cf-3c68-4f76-9087-575db8d19cd2
date added to LUP
2022-07-25 18:19:58
date last changed
2023-11-09 15:22:49
@article{363e19cf-3c68-4f76-9087-575db8d19cd2,
  abstract     = {{Background<br/>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.<br/><br/>Methods<br/>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.<br/><br/>Results<br/>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.<br/><br/>Conclusion<br/>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.}},
  author       = {{Demircan, Kamil and Sun, Qian and Bengtsson, Ylva and Seemann, Petra and Vallon-Christersson, Johan and Malmberg, Martin and Saal, Lao and Ryden, Lisa and Minich, Waldemar B. and Borg, Åke and Manjer, Jonas and Schomburg, Lutz}},
  issn         = {{2213-2317}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Elsevier}},
  series       = {{Redox Biology}},
  title        = {{Autoimmunity to selenoprotein P predicts breast cancer recurrence}},
  url          = {{http://dx.doi.org/10.1016/j.redox.2022.102346}},
  doi          = {{10.1016/j.redox.2022.102346}},
  volume       = {{53}},
  year         = {{2022}},
}