Marques Oriana, Rosa Ana, Leite Luciana, Faustino Paula, Rêma Alexandra, Martins da Silva Berta, Porto Graça, Lopes Carlos
Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Lab Immunogenetics & Autoimmu and NeuroScien, UMIB, ICBAS, University of Porto, Porto, Portugal.
Cancer Microenviron. 2016 Dec;9(2-3):85-91. doi: 10.1007/s12307-016-0191-4. Epub 2016 Dec 27.
The association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients' HFE genotype. Within the group of patients with invasive carcinoma, those carrying the p.Cys282Tyr variant in heterozygosity presented a higher expression of hepcidin in lymphocytes and macrophages than wild-type or p.His63Asp carriers. An increased expression of TfR1 was also observed in all the cell types analyzed but only in p.Cys282Tyr/p.His63Asp compound heterozygous patients. A differential impact of the two HFE variants was further noticed with the observation of a significantly higher percentage of p.Cys282Tyr heterozygous patients presenting tissue iron deposition in comparison to p.His63Asp heterozygous. In the present cohort, no significant associations were found between HFE variants and classical clinicopathological markers of breast cancer behavior and prognosis. Although limited by a low sampling size, our results provide a new possible explanation for the previously reported impact of HFE major variants on breast cancer progression, i.e., not by influencing systemic iron homeostasis but rather by differentially modulating the local cellular expression of iron-related proteins and tissue iron deposition.
HFE（高铁FE）主要变体与乳腺癌风险及行为之间的关联长期以来一直是讨论的话题。然而，它们对乳腺癌组织中铁相关蛋白表达的影响从未得到探讨。在本研究中，对一组乳腺癌患者样本中的铁调素、铁转运蛋白1、转铁蛋白受体1（TfR1）和铁蛋白表达以及组织铁沉积进行了评估，并根据患者的HFE基因型进行了分析。在浸润性癌患者组中，杂合携带p.Cys282Tyr变体的患者，其淋巴细胞和巨噬细胞中铁调素的表达高于野生型或p.His63Asp携带者。在所有分析的细胞类型中也观察到TfR1表达增加，但仅在p.Cys282Tyr/p.His63Asp复合杂合患者中。通过观察发现，与p.His63Asp杂合患者相比，p.Cys282Tyr杂合患者出现组织铁沉积的比例显著更高，进一步注意到这两种HFE变体的不同影响。在本队列中，未发现HFE变体与乳腺癌行为和预后的经典临床病理标志物之间存在显著关联。尽管受样本量少的限制，但我们的结果为先前报道的HFE主要变体对乳腺癌进展的影响提供了一种新的可能解释，即不是通过影响全身铁稳态，而是通过差异调节铁相关蛋白的局部细胞表达和组织铁沉积。
