Roles of cathepsin S expression levels on the prognosis and tumour microenvironment in clear cell renal cell carcinoma

Xiang Wang; Bei Feng; Hai-Ying Guo; Fei-Fei Yao; Hui-Nan Song; Xi-Yue Wang; Xiao-Chen Sun; Kai Wang; Yu-Chen Ge; Rui Cui

doi:10.1007/s12672-024-01547-3

Roles of cathepsin S expression levels on the prognosis and tumour microenvironment in clear cell renal cell carcinoma

Discov Oncol. 2024 Nov 21;15(1):690. doi: 10.1007/s12672-024-01547-3.

Authors

Xiang Wang^#^{1

2

3}, Bei Feng^#^{4

2

3}, Hai-Ying Guo^{2

3}, Fei-Fei Yao², Hui-Nan Song², Xi-Yue Wang², Xiao-Chen Sun^{2

3}, Kai Wang^{2

3}, Yu-Chen Ge^{2

3}, Rui Cui⁵

Affiliations

¹ Department of Nephrology, The First People's Hospital in Jinzhou, Dalian, China.
² Department of Nephrology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
³ NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
⁴ Department of Nephrology, Jingzhou Central Hospital, Hubei, China.
⁵ Department of Nephrology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. CuiRui0219@163.com.

^# Contributed equally.

PMID: 39570472
DOI: 10.1007/s12672-024-01547-3

Abstract

Background: Increasing evidence suggests a link between the enzyme cathepsin S (CTSS) and tumour development. However, the potential involvement and molecular functions of CTSS in clear cell renal cell carcinoma (ccRCC) remain unclear.

Methods: We downloaded original data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated them using R. Kaplan-Meier plots of integrated expression scores were used to analyse survival outcomes. Additionally, we investigated mRNA expression, clinicopathological features, immune infiltrates, and single-cell sequencing analysis of CTSS in ccRCC. In vitro experiments were conducted with qRT-PCR and IHC staining.

Results: CTSS transcriptomic and proteomic levels were higher in ccRCC than in para-cancerous tissues. Low CTSS expression was correlated with poor prognosis in patients with ccRCC. Our data demonstrated that the expression of CTSS was strongly correlated with immune cell infiltration levels and gene markers of immune cells, chemokines, and receptors. Single-cell sequencing analysis demonstrated that CTSS expression was detectable in monocytes/macrophages. Finally, certain chemicals were confirmed to affect CTSS expression.

Conclusion: Our findings indicate that CTSS offers promise as a prognostic biomarker and novel immune-related therapeutic target for ccRCC.

Keywords: Cathepsin S; CcRCC; Immune infiltration; Prognosis; Tumour microenvironment.