Semlali Abdelhabib, Jalouli Maroua, Parine Narasimha Reddy, Al Amri Abdullah, Arafah Maha, Al Naeem Abdulrahman, Abdullah Ajaj Sanaa, Rouabhia Mahmoud, Alanazi Mohammad Saud
Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec, QC, Canada.
Onco Targets Ther. 2017 Feb 24;10:1207-1216. doi: 10.2147/OTT.S112165. eCollection 2017.
The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.
本研究旨在调查沙特阿拉伯人群中Toll样受体4（TLR - 4）常见多态性与乳腺癌发生之间的关联。使用127例乳腺癌患者和117例对照研究了4种TLR - 4多态性（rs2770150、rs10759931、rs10759932和rs4986790）。通过使用特异性抗TLR - 4抗体的免疫组织化学方法，以组织微阵列形式在70个临床乳腺样本的大型队列中测定了乳腺肿瘤和匹配的正常乳腺组织中TLR - 4蛋白的相对表达。我们的结果表明，与正常情况相比，雌激素受体（ER）阳性的绝经后乳腺癌患者中TLR - 4表达增加。我们还证明，与对照组（26.7%）相比，患者中发现单核苷酸多态性的G等位基因频率显著更高（36.3%），这表明这种多态性与该种族人群中乳腺癌的发生密切相关。此外，TLR - 4多态性在48岁以上的患者中与乳腺癌高度相关。在ER阴性患者组中也发现TLR - 4多态性与这种恶性肿瘤有关。我们的结果首先表明，TLR - 4基因表达的变化可能影响乳腺癌的发生，其次表明TLR - 4基因多态性与ER状态之间存在密切的关联。我们的研究为更好地理解TLR - 4多态性在乳腺肿瘤发生中的意义以及最终将其用作癌症生物标志物提供了支持。
