Panigoro Sonar S, Paramita Rafika I, Wanandi Septelia I, Fadilah Fadilah, Wibisana I Gng, Sutandyo Noorwati
Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Narra J. 2025 Apr;5(1):e1364. doi: 10.52225/narra.v5i1.1364. Epub 2024 Jan 30.
Breast cancer subtypes can be categorized based on their gene expression profiles using immunohistochemistry into Luminal A, Luminal B, human epidermal growth factor receptor 2-positive (HER), and triple-negative breast cancer (TNBC) subtypes. However, immunohistochemistry has certain limitations that can lead to misclassification. DNA methylation is an epigenetic modification, and changes in the promoter region can alter gene expression and the quantity of functional protein synthesized, disrupting gene function. The aim of this study was to identify DNA methylation biomarkers for subtype classification in breast cancer using microarray and methylation-specific polymerase chain reaction (MSP) methods. DNA samples were extracted, subjected to bisulfite conversion and then used for both the microarray and MSP methods. This study successfully identified differentially methylated CpGs (DMCs) as biomarker for each subtype classification of breast cancer: Luminal A (hypermethylation of gene; cg14397888), Luminal B (hypomethylation of gene; cg14397888), HER (hypermethylation of gene; cg25910261), and TNBC (hypomethylation of gene; cg15652532). The DMC biomarker found for the HER subtype, hypermethylation in the gene (cg25910261), has the potential to be used by healthcare providers to identify HER patients and provide the HER2-targeted therapy to improve the patient's survival. In addition, our developed MSP method could produce an effective diagnostic tool for classifying the Luminal A and Luminal B subtypes, with accuracies of 75% and 76%, respectively.
乳腺癌亚型可通过免疫组织化学根据其基因表达谱分为腔面A型、腔面B型、人表皮生长因子受体2阳性（HER）型和三阴性乳腺癌（TNBC）亚型。然而，免疫组织化学存在某些局限性，可能导致错误分类。DNA甲基化是一种表观遗传修饰，启动子区域的变化可改变基因表达和合成的功能性蛋白质数量，从而破坏基因功能。本研究的目的是使用微阵列和甲基化特异性聚合酶链反应（MSP）方法鉴定用于乳腺癌亚型分类的DNA甲基化生物标志物。提取DNA样本，进行亚硫酸氢盐转化，然后用于微阵列和MSP方法。本研究成功鉴定出差异甲基化的CpG（DMC）作为乳腺癌各亚型分类的生物标志物：腔面A型（基因cg14397888高甲基化）、腔面B型（基因cg14397888低甲基化）、HER型（基因cg25910261高甲基化）和TNBC型（基因cg15652532低甲基化）。为HER亚型发现的DMC生物标志物，即基因（cg25910261）高甲基化，有可能被医疗保健提供者用于识别HER患者并提供HER2靶向治疗以提高患者生存率。此外，我们开发的MSP方法可为腔面A型和腔面B型亚型的分类产生一种有效的诊断工具，准确率分别为75%和76%。
