Sialyl-Tn expression correlates with reduced c-Myc and immune modulation in triple negative breast cancer

Triple negative breast cancer (TNBC) is an aggressive, heterogeneous cancer with lack of targeted therapies. The cancer-associated sialyl-Tn (STn) antigen has a significant role in cancer, yet its involvement in TNBC remains unexplored. This study investigates STn’s role in TNBC, analysing its expression in the primary tumour tissues of 126 TNBC patients alongside other biomarkers and clinical features. STn was detected in 23.8% of cases, exhibiting significantly reduced survival and lower c-Myc expression. Additionally, data from The Cancer Genome Atlas (TCGA) TNBC cohort confirmed this association, showing that high levels of ST6GALNAC1, gene encoding the enzyme responsible for the STn synthesis, were inversely correlated with MYC expression and positively associated with TGF-β signalling genes and immunosuppressive cell infiltrates, such as macrophages M2 and regulatory T cells. Accordingly, STn-positive TNBC cell lines exhibited increased proliferation and lower c-Myc protein expression, while co-culture with macrophages enhanced M2 polarization. This study discloses, for the first time, a subgroup of TNBC patients expressing the STn antigen, pointing to an immunosuppressive environment that may lead to the observed negative correlation between STn and c-Myc. These results introduce STn as a potential prognostic biomarker and therapeutic target, laying the groundwork for more effective, personalized treatments for TNBC.