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 a hallmark of 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 castration-resistant prostate cancer (CRPC), and in patient-derived xenograft (PDX) tissues. 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 the liver and bone shows sTn is expressed in 37.5% of cases. Furthermore, sTn is expressed in nearly half of the PDX models tested and was found to be broadly androgen-regulated. These findings identify sTn as a potential prognostic biomarker and therapeutic target in prostate cancer and lay the groundwork for the development of sTn-targeted precision therapies for advanced disease.