Sialic acid metabolism-related gene CTSA drives prostate cancer immunosuppression and tumor progression

Prostate cancer (PCa) is the second most common cancer in males. Androgen deprivation therapy (ADT) serves as the primary non-surgical treatment approach. However, the frequent progression to castration-resistant PCa after ADT drives the need for new therapeutic modalities in PCa. In recent years, tumor immunotherapy has made significant progress in the treatment of many tumors, but clinically, only a small number of PCa patients benefit from immunotherapy because of cold immune microenvironment. Many studies have shown that sialic acid metabolism is related to the immunosuppressive tumor microenvironment (TME). Utilizing RNA sequencing data in The Cancer Genome Atlas (TCGA), we investigated the association between sialic acid metabolism-related genes and the carcinogenesis of PCa. Based on both transcriptomic and proteomics data, we discovered that the high expression of the cathepsin A (CTSA) is associated with the tumorigenesis and poor prognosis of PCa. Further pathway enrichment analysis revealed that CTSA is related to several immunity-associated pathways. We validated the role of CTSA in the TME of PCa using single-cell RNA sequencing. Through animal experiments and fluorescence staining, we demonstrated that CTSA contributes to the formation of immunosuppressive TME. Targeting CTSA provides a potential effective for PCa treatment and enhances immunotherapy efficacy.