Mohsin Mohammed Dlshad, Salihi Abbas
Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, 44001, Iraq.
Center of Research and Strategic Studies, Lebanese French University, Erbil, Kurdistan Region, 44002, Iraq.
Mol Biol Rep. 2025 May 19;52(1):467. doi: 10.1007/s11033-025-10584-2.
Breast cancer (BC) is the primary cause of cancer-related death among women globally, highlighting the importance of the identification of novel biomarkers for early detection and prognosis. This study investigates the impact of NOS3 (endothelial nitric oxide synthase) and SOD1 (superoxide dismutase 1) gene polymorphisms on BC development, focusing on their associations with oxidative stress and tumor progression.
A case-control study involving 30 BC patients and 30 healthy controls was conducted. Mutations in NOS3 and SOD1 genes were identified using sanger sequencing. ELISA was used to measure oxidative stress markers such peroxynitrite (ONOO) and superoxide dismutase (SOD). To investigate functional associations, protein-protein interaction networks were examined using the GENEMANIA database.
The study identified 32 polymorphisms in the NOS3 gene and 16 polymorphisms in the SOD1 gene, as well as nine amino acids alterations predicted in SOD1 gene. In comparison to controls, BC patients had higher levels of ONOO- (0.095 ± 0.048 ng/L vs. 0.048 ± 0.057 ng/L, p < 0.0001) and SOD (0.074 ± 0.033 ng/ml vs. 0.043 ± 0.045 ng/ml, p < 0.001). GENEMANIA analysis showed the interactions among NOS3, SOD1, and oxidative stress-related genes, highlighting their significance in cellular redox balance.
These findings suggest that NOS3 and SOD1 polymorphisms may contribute to BC pathogenesis, as supported by the observed oxidative stress alterations (ONOO- and SOD levels). Additional validation in larger cohorts is needed to confirm their potential as biomarkers for risk evaluation and clinical advancement. The study enhances understanding of the genetic and oxidative stress mechanisms in cancer biology and identifies potential therapeutic targets for further investigation.
乳腺癌（BC）是全球女性癌症相关死亡的主要原因，这凸显了识别用于早期检测和预后的新型生物标志物的重要性。本研究调查了NOS3（内皮型一氧化氮合酶）和SOD1（超氧化物歧化酶1）基因多态性对BC发生发展的影响，重点关注它们与氧化应激和肿瘤进展的关联。
进行了一项病例对照研究，纳入30例BC患者和30例健康对照。使用桑格测序法鉴定NOS3和SOD1基因的突变。采用酶联免疫吸附测定法（ELISA）测量氧化应激标志物，如过氧亚硝酸根（ONOO）和超氧化物歧化酶（SOD）。为了研究功能关联，使用GENEMANIA数据库检查蛋白质-蛋白质相互作用网络。
该研究在NOS3基因中鉴定出32个多态性位点，在SOD1基因中鉴定出16个多态性位点，以及SOD1基因中预测的9个氨基酸改变。与对照组相比，BC患者的ONOO-水平较高（0.095±0.048 ng/L对0.048±0.057 ng/L，p<0.0001），SOD水平也较高（0.074±0.033 ng/ml对0.043±0.045 ng/ml，p<0.001）。GENEMANIA分析显示NOS3、SOD1和氧化应激相关基因之间存在相互作用，突出了它们在细胞氧化还原平衡中的重要性。
这些发现表明，NOS3和SOD1基因多态性可能与BC发病机制有关，观察到的氧化应激改变（ONOO-和SOD水平）支持了这一点。需要在更大的队列中进行进一步验证，以确认它们作为风险评估和临床进展生物标志物的潜力。该研究增进了对癌症生物学中遗传和氧化应激机制的理解，并确定了有待进一步研究的潜在治疗靶点。
