Alhaddad Lama, Saifo Maher, Alsayed Ranwa
Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, Syrian Arab Republic.
Department of Oncology, Damascus University, Damascus, Syrian Arab Republic.
Discov Oncol. 2025 May 31;16(1):972. doi: 10.1007/s12672-025-02799-3.
Cancer cells have a greater requirement for iron because of their continuous and rapid proliferation. To do that, iron homeostasis is altered in cancer cells to meet this excessive demand. Transferrin (TF) and lipocalin 2 (LCN2) are proteins that play essential roles in transporting and delivering iron into cells. The aim of this study was to investigate the serum levels of transferrin and lipocalin 2 in Syrian breast cancer patients, and compare them with those in a control group and their correlation with the tumor state and characteristics. This case‒control study included 80 Syrian women divided into two groups: a group of patients with breast cancer who were newly diagnosed via biopsy (n = 40), and a control group of healthy women (n = 40). Serum transferrin levels were measured via an immunoturbidimetric assay and serum levels of lipocalin 2 were measured via an enzyme-linked immunosorbent assay (ELISA). Compared with the control group, the case group presented lower levels of Lipocalin 2, but serum LCN2 levels were correlated with estrogen and progesterone receptor (ER,PR) negative status (r = -0.330, p-value = 0.038) and (r = -0.441, p-value = 0.004) respectively. However, transferrin levels were correlated only with progesterone receptor status. Interestingly, there was a negative correlation between serum lipocalin 2 and transferrin serum levels (r = -0.416, p-value = 0.008). This study revealed that serum lipocalin 2 levels decrease in breast cancer patients with increased tumor expression of the ER and PR receptors, it also indicates the collaboration and the cross-talk of iron transport proteins to deliver it to cancer cells. This suggests the importance of iron transport proteins as novel biomarkers and perhaps as therapeutic targets for aggressive subtypes of breast cancer (ER-negative and PR-negative subtypes).
由于癌细胞持续快速增殖,它们对铁的需求量更大。为此,癌细胞中的铁稳态会发生改变以满足这种过量需求。转铁蛋白(TF)和脂质运载蛋白2(LCN2)是在将铁运输并递送至细胞过程中发挥重要作用的蛋白质。本研究的目的是调查叙利亚乳腺癌患者血清中转铁蛋白和脂质运载蛋白2的水平,并将其与对照组进行比较,以及研究它们与肿瘤状态和特征的相关性。这项病例对照研究纳入了80名叙利亚女性,分为两组:一组是经活检新诊断出的乳腺癌患者(n = 40),另一组是健康女性对照组(n = 40)。通过免疫比浊法测量血清转铁蛋白水平,通过酶联免疫吸附测定(ELISA)测量血清脂质运载蛋白2水平。与对照组相比,病例组的脂质运载蛋白2水平较低,但血清LCN2水平分别与雌激素和孕激素受体(ER、PR)阴性状态相关(r = -0.330,p值 = 0.038)和(r = -0.441,p值 = 0.004)。然而,转铁蛋白水平仅与孕激素受体状态相关。有趣的是,血清脂质运载蛋白2与血清转铁蛋白水平之间存在负相关(r = -0.416,p值 = 0.008)。本研究表明,ER和PR受体肿瘤表达增加的乳腺癌患者血清脂质运载蛋白2水平降低,这也表明了铁转运蛋白在将铁递送至癌细胞过程中的协作和相互作用。这表明铁转运蛋白作为新型生物标志物以及可能作为侵袭性乳腺癌亚型(ER阴性和PR阴性亚型)治疗靶点的重要性。