低血清硒和某些硒蛋白基因表达的改变与乳腺癌预后不良相关。硒蛋白基因表达严格依赖于硒的可用性，因此循环硒可能与肿瘤硒蛋白基因表达相互作用。然而，到目前为止还没有进行过相匹配的分析。本研究纳入了1453例新诊断的乳腺癌患者，这些患者来自多中心前瞻性瑞典癌组学分析网络-乳腺研究。在诊断时分析了总血清硒、硒蛋白P和谷胱甘肽过氧化物酶3。对相匹配的肿瘤组织进行了大规模RNA测序。采用完全调整的Cox回归模型，并引入交互项来检测循环硒与肿瘤硒蛋白mRNA表达和死亡率之间的剂量依赖性相互作用。在大约9年的随访期间记录了237例死亡。所有三个血清硒生物标志物均呈正相关（p<0.001）。除GPX6外，所有硒蛋白均在肿瘤组织中表达。单细胞RNA测序揭示了肿瘤微环境中异质的表达模式。循环硒与肿瘤SELENOW和SELENON的表达呈正相关（p<0.001）。在完全调整的模型中，DIO1、DIO3和SELENOM与死亡率的关联受到循环硒的剂量依赖性修改（p<0.001，p=0.020，p=0.038）。随着硒的增加，DIO1和SELENOM与较低的死亡率相关，而DIO3的表达与较高的死亡率相关。DIO1与较低死亡率的关联仅在高硒（高于中位数，70.36 µg/L）患者中观察到，对数(FPKM+1)每单位增加的风险比（95%CI）为0.70（0.50-0.98）。这是首次对血清硒与乳腺癌硒转录组的无偏分析，结果发现硒对DIO1、SELENOM和DIO3与预后的关联具有修饰效应。在DIO1表达的肿瘤患者中考虑硒替代可能有助于改善生存率。© 2023. BioMed Central Ltd.，Springer Nature的一部分。

Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date.This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network - Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality.237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50-0.98).This first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival.© 2023. BioMed Central Ltd., part of Springer Nature.