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.
Redox Biol. 2022 Jul;53:102346. doi: 10.1016/j.redox.2022.102346. Epub 2022 May 25.
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.
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.
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.
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.
低浓度的血清硒（Se）及其主要载体硒蛋白 P（SELENOP）与乳腺癌诊断后的不良预后相关。最近，在健康受试者和甲状腺疾病患者中发现了具有拮抗 SELENOP 摄取特性的天然自身抗体（aAb）。鉴于其潜在的运输干扰特性，我们假设具有 SELENOP-aAb 的乳腺癌患者可能预后不良。
在多中心 SCAN-B 研究中，对 1988 例新诊断为乳腺癌的患者的血清样本中测定了 SELENOP-aAb 以及血清 Se、SELENOP 和 GPX3 活性。对患者进行了约 9 年的随访，并应用多变量 Cox 回归模型评估危险比。
应用基于异常值检测的截止值，我们确定了 7.65%的 SELENOP-aAb 患者。自身抗体滴度与总 Se 和 SELENOP 浓度呈正相关，但与 GPX3 活性无关，这支持 SELENOP-aAb 对 Se 转运的负作用。SELENOP-aAb 与年龄相关，但与肿瘤特征无关。在充分调整潜在混杂因素后，SELENOP-aAb 与更高的复发风险相关，HR（95%CI）=1.87（1.17-2.99），尤其是在 Se 浓度低的患者中，HR（95%CI）=2.16（1.20-3.88）。SELENOP-aAb 与复发和死亡率的相关性呈线性和剂量依赖性，充分调整后的 HR（95%CI）每增加 1. log 为 1.25（1.01-1.55）和 1.31（1.13-1.51）。
我们的结果表明，SELENOP-aAb 在乳腺癌中具有预后和病理生理学相关性，对其他恶性肿瘤可能具有相关性。在诊断时评估 SELENOP-aAb 可识别出预后明显较差的患者，独立于既定的预后因素，这些患者可能对 Se 补充反应良好。
