POL Scientific / Bladder / Volume 12 / Issue 1 / DOI: 10.14440/bladder.2024.0057
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RESEARCH ARTICLE

Expression profiles and clinical significance of cystatin family genes in transitional cell carcinoma of the urinary bladder

Haixia Xu1 ,  Wang Liu2 ,  Xiangxing Kuang3 ,  Jiang Zhao4 ,  Xiangwei Wang4 ,  Benyi Li2*
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1 Department of Medical Oncology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guandong 518035, China
2 Department of Urology, School of Medicine, The University of Kansas Medical Center, Kansas 66160, United States of America
3 Department of Urology, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, Guangdong 510803, China
4 Department of Urology, School of Medicine, Guangdong Medical University, Zhanjiang, Guangdong 524001, China
Bladder 2025 , 12(1), e21200035; https://doi.org/10.14440/bladder.2024.0057
Submitted: 9 November 2024 | Revised: 2 December 2024 | Accepted: 11 February 2025 | Published: 13 March 2025
© 2025 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/ )
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Abstract

Background: Cystatins, encoded by the CST gene family, are a superfamily of cysteine protease inhibitors involved in a wide array of biological functions, including immune modulation and antimicrobial defense. Cystatin proteins are implicated in tumor progression through multiple mechanisms. However, their roles in bladder cancer remain poorly understood. Objective: This study examined the expression profiles of the cystatin family genes and analyzed their correlation with clinicopathological parameters using the Cancer Genome Atlas Bladder Cancer RNA-seq dataset. Methods: The RNAseq dataset derived from the Cancer Genome Atlas project was utilized for the gene expression analysis on the XIANTAO online platform. The UALCAN online platform was used for the analysis of gene expression in molecular subgroups. The differences among various subgroups were statistically analyzed to define the significance. Results: Our results showed that CST3, CST6, CST7, CSA, and CSTB were predominantly expressed in bladder tissues. CST6, CSTA, and CSTB were upregulated, while CST3 and CST7 were downregulated in bladder cancer tissues. CST1 and CST2 were moderately expressed but significantly upregulated in malignant tissues. Specifically, malignant tissues could be effectively differentiated from benign tissues in terms of CST1 expression, with an area under the curve value of 0.904. Upregulation of CST2 was associated with multiple clinicopathological parameters, while downregulation of CST3 was correlated with unfavorable outcomes in overall survival, disease-specific survival, and progression-free survival. Further analysis revealed that CST7 expression bore an association with immune infiltration, suggesting that it plays a role in the modulation of immune cells. Conclusion: CST genes were distinctly expressed in bladder cancer with different clinical implications.

Keywords
Bladder cancer
Cystatin family genes
Immune infiltration
Survival outcomes
Disease progression
DNA methylation
Funding
None.
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Conflict of interest
The authors declared no commercial or financial relationships construed as potential conflicts of interest.
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Bladder, Electronic ISSN: 2327-2120 Print ISSN: TBA, Published by POL Scientific
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