Multi-Omics Analysis of ST3GAL4-Mediated Lacto/Neolacto Glycosphingolipid Metabolism Reveals Immune Evasion and Poor Prognosis in TNBC

The Lacto/Neolacto glycosphingolipid metabolism pathway was markedly activated in TNBC compared to adjacent and non-TNBC tissues, correlating with worse prognosis. Machine learning identified ST3GAL4 as the core enzyme within this pathway. High ST3GAL4 expression was associated with increased infiltration of regulatory T cells (Tregs) and M2 macrophages, reduced CD8⁺ T-cell activity, and enhanced epithelial–mesenchymal transition. Spatial transcriptomics confirmed localized enrichment of immunosuppressive cells in ST3GAL4-high regions. IHC validation demonstrated that ST3GAL4 overexpression in TNBC tissues predicts poor clinical outcomes.

与癌旁组织及非三阴性乳腺癌（TNBC, Triple-Negative Breast Cancer）组织相比，乳糖/新乳糖鞘糖脂代谢通路在三阴性乳腺癌组织中显著激活，且与不良预后相关。机器学习方法将ST3GAL4鉴定为该通路中的核心酶。ST3GAL4高表达与调节性T细胞（Tregs）和M2型巨噬细胞浸润增加、CD8⁺ T细胞活性降低以及上皮间质转化（EMT, Epithelial-Mesenchymal Transition）增强密切相关。空间转录组学证实，ST3GAL4高表达区域存在免疫抑制细胞的局部富集。免疫组化（IHC, Immunohistochemistry）验证结果表明，三阴性乳腺癌组织中ST3GAL4过表达可预测不良临床结局。