AccScience Publishing / TD / Online First / DOI: 10.36922/TD025290065
ORIGINAL RESEARCH ARTICLE

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

Jiahao Lei1 Shuntian Gao2 Yao He3 Dongxin An1 Rui Sun1 Lingwu Chen1* Ren Liu1* Zongren Wang1*
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1 Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
2 Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
Tumor Discovery, 025290065 https://doi.org/10.36922/TD025290065
Received: 14 July 2025 | Revised: 14 November 2025 | Accepted: 17 December 2025 | Published online: 2 January 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

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.

Graphical abstract
Keywords
Sialic acid
Cathepsin A
Prostate cancer
Tumor microenvironment
Funding
This work was supported by grants from the National Natural Science Foundation of China (82372056, 82273299, 82403533), the China Postdoctoral Science Foundation (2024M763761), and the Sun Yat-sen University First Affiliated Hospital Kelin Emerging Talent Program (R07019 to Z.W.).
Conflict of interest
The authors declare that they have no competing interests.
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