Abstract
SEPT9 methylation has been closely linked to breast cancer, yet its role in differentiating disease stages remains unclear. In particular, Few studies previously have examined differences in SEPT9 methylation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), or among DCIS lesions of varying nuclear grades. This study investigated SEPT9 methylation across 105 breast cancer cases, classified into pure DCIS, DCIS with invasive components (DCIS-INV), IDC alone, and metastatic breast cancer (MBC). Methylation levels were measured using real-time PCR, and in vitro experiments were conducted using MCF-7 and T47D cell lines treated with decitabine to explore the relationship between methylation and microtubule stability. SEPT9 methylation was significantly elevated in cancer cells compared to normal breast epithelium, with positivity rates of 90.6% in DCIS-INV, 77.8% in IDC, and 79.2% in MBC, versus only 18.2% in pure DCIS. SEPT9 methylation was negtive in low-grade DCIS and positive in 28.6% of intermediate- to high-grade cases. Positive methylation was significantly associated with high Ki-67 expression and lymph node metastasis (P < 0.05), but showed no correlation with age, menopausal status, tumor size, or hormone receptor status. Additionally, decitabine treatment induced a reduction in SEPT9 methylation levels, which affects microtubule stability, suggesting a potential mechanistic link to tumor invasion. These findings indicate that SEPT9 methylation is a promising biomarker for distinguishing invasive breast cancer from DCIS and for identifying high-risk DCIS lesions with greater potential for progression.