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.