Åke Borg
Principal investigator
Autoimmunity to selenoprotein P predicts breast cancer recurrence
Author
Summary, in English
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.
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.
Department/s
- Surgery
- LUCC: Lund University Cancer Centre
- Breastcancer-genetics
- Translational Oncogenomics
- The Liquid Biopsy and Tumor Progression in Breast Cancer
- Breast Cancer Surgery
- Familial Breast Cancer
- EpiHealth: Epidemiology for Health
Publishing year
2022-05-25
Language
English
Publication/Series
Redox Biology
Volume
53
Document type
Journal article
Publisher
Elsevier
Topic
- Cancer and Oncology
Status
Published
Project
- Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
Research group
- Surgery
- Translational Oncogenomics
- The Liquid Biopsy and Tumor Progression in Breast Cancer
- Breast Cancer Surgery
- Familial Breast Cancer
ISBN/ISSN/Other
- ISSN: 2213-2317