Comprehensive profiling reveals Sialyl-Tn upregulation and prognostic value in prostate cancer

Prostate cancer is a common cancer in males and there is an urgent unmet clinical need to identify new therapies for advanced disease. Aberrant glycosylation is common in prostate cancer and plays a functional role in disease progression. The sialyl-Tn antigen (sTn) has been widely studied in cancer, yet its involvement in prostate cancer remains relatively unexplored. Here, we utilise a novel anti-sTn antibody (L2A5) to comprehensively monitor sTn expression levels in clinical prostate cancer tissues encompassing normal, benign, primary, metastatic castrate-resistant prostate cancer (CRPC), and patient-derived xenografts (PDXs). We show that while sTn is detected at low or negligible levels in normal prostate tissues, it is expressed in 44% of prostate tumours, and prostate cancer patients with high sTn levels have significantly poorer survival times. Analysis of metastatic therapy resistant prostate-derived tumours growing in liver and bone, shows sTn is expressed in 37.5% of cases. Furthermore, we show sTn is expressed in nearly half of PDXs tested, supporting the use of PDX models as tools for testing anti-sTn therapeutic strategies. These findings identify sTn as potential prognostic biomarker and therapeutic target in prostate cancer and lay the groundwork for the development of sTn-targeted precision therapies for advanced disease.