Autoimmunity to selenoprotein P predicts breast cancer recurrence

Redox Biology

Qian Sun¹  Martin Malmberg²  Lisa Rydén³  Petra Seemann⁴  Åke Borg⁴  Lutz Schomburg⁵  Lao H. Saal⁵  Waldemar B. Minich⁵  Ylva Bengtsson⁶  Kamil Demircan⁶  Johan Vallon-Christersson⁶  Jonas Manjer⁶ 

[1] Berlin Institute of Health (BIH), Biomedical Innovation Academy (BIA), Berlin, Germany;selenOmed GmbH, Berlin, Germany;Department of Oncology, Skåne University Hospital, Lund, Sweden;Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, 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;

关键词: SELENOP;    Glutathione peroxidase;    Selenium;    Prognosis;    Cohort study;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown