Prognostic value and immunological role of cathepsin S gene in pan‑cancer

Liang,Shengsheng; Dang,Bowen; Chen,Shaohua; Mi,Hua

doi:10.3892/ol.2023.14175

Prognostic value and immunological role of cathepsin S gene in pan‑cancer

Authors:
- Shengsheng Liang
- Bowen Dang
- Shaohua Chen
- Hua Mi
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Affiliations: Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Urology, The First People's Hospital of Yulin, Yulin, Guangxi Zhuang Autonomous Region 537000, P.R. China, Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
Published online on: December 4, 2023 https://doi.org/10.3892/ol.2023.14175
Article Number: 41
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The cathepsin S (CTSS) gene encodes a lysine cysteine protease and serves an important role in the development of autoimmune diseases, inflammation and nervous system diseases. Furthermore, CTSS is implicated in tumor invasion and metastasis by the induction of tumor angiogenesis and the degradation of the tumor extracellular matrix. Nevertheless, the precise impact of CTSS on predicting pan‑cancer prognosis and its influence on the tumor microenvironment and immune infiltration in human cancers remains unknown. This present study employed a comprehensive array of bioinformatic methods to evaluate the expression of CTSS and its associations with prognosis, clinicopathological characteristics, tumor microenvironment, tumor immune infiltration, tumor mutational burden and microsatellite instability across numerous cancer types. The current study demonstrated abnormal expression and distinct genomic alteration profiles of CTSS in many of the cancers tested. Furthermore, CTSS expression exhibited close associations with the prognosis of numerous cancers. High CTSS expression was significantly associated with better overall survival and disease‑specific survival in bladder urothelial carcinoma (BLCA) and skin cutaneous melanoma (SKCM) but worse outcomes in brain lower grade glioma (LGG) and uveal melanoma (UVM). Moreover, CTSS demonstrated significant correlations with tumor mutational burden and microsatellite instability in 8 and 12 cancer types respectively, as well as different responses in immunotherapy sub‑cohorts, especially in melanoma and bladder cancers. CTSS expression showed a positive correlation with stromal and immune cell scores in the four aforementioned cancers. Moreover, CTSS expression was correlated with the number of infiltrating CD8⁺ T cells, CD4⁺ T cells and macrophages. Conversely, CTSS was negatively associated with resting Mast cells, resting NK cells and resting memory CD4⁺ T cell infiltration in BLCA, SKCM and kidney renal clear cell carcinoma (KIRC). Furthermore, CTSS expression was correlated with immune‑related gene expression, notably PDCD1, LAG3, PDCD1 and TIGIT in BLCA, KIRC, SKCM, LGG and UVM. Functional enrichment analysis suggested that CTSS could drive a dynamic adjustment of biological functions and pathways in BLCA, SKCM, LGG and UVM, including immune response regulating signaling pathways, regulation of lymphocyte activation and T cell receptor singling pathways. The current study suggested that CTSS could be an essential biomarker for prognosis and immune infiltration features in multiple cancers.

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