Autoimmunity to selenoprotein P predicts breast cancer recurrence.

Kamil Demircan, Qian Sun, Ylva Bengtsson, Petra Seemann, Johan Vallon-Christersson, Martin Malmberg, Lao H Saal, Lisa Rydén, Waldemar B Minich, Åke Borg, Jonas Manjer, Lutz Schomburg

Journal: Redox biology 2022;53():102346

PMID: 35636018

Free Full Text on Elsevier Science View on PubMed

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 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.

Address: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Biomedical Innovation Academy (BIA), Berlin, Germany.; Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany.; Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.; Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany; selenOmed GmbH, Berlin, Germany.; Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.; Department of Oncology, Skåne University Hospital, Lund, Sweden.; Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany. Electronic address: [email protected].

DOI: 10.1016/j.redox.2022.102346

Link outs

Free resources

Full Text Sources:

Medical:

Miscellaneous:

https://assays.cancer.gov/non-CPTAC-3540

MeSH Terms: Autoantibodies, Autoimmunity, Breast Neoplasms, Female, Humans, Selenium, Selenoprotein P