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

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.