Comprehensive Profiling Reveals Sialyl‐Tn Upregulation and Prognostic Value in Prostate Cancer

ABSTRACT

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.