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

## TL;DR

This study finds that sialyl-Tn (STn) is linked to worse survival and immune suppression in a subgroup of triple negative breast cancer patients.

## Contribution

The study identifies STn as a novel prognostic biomarker and potential therapeutic target in triple negative breast cancer.

## Key findings

- STn was detected in 23.8% of triple negative breast cancer cases and correlated with reduced survival and lower c-Myc expression.
- High ST6GALNAC1 levels were inversely correlated with MYC and positively associated with immunosuppressive cell infiltrates like M2 macrophages and regulatory T cells.
- STn-positive cell lines showed increased proliferation and lower c-Myc protein, with macrophage co-culture enhancing M2 polarization.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-025-21496-3.