The oncogenic functions of SPARCL1 in bladder cancer
Changjiu Li1, Hui Yuan2,3, Jun Chen2
1Department of Urology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
Abstract:
Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) belongs to the SPARC family of matricellular proteins. However, underlying functions of SPARCL1 in bladder cancer (BCa) remain understudied. We performed an integrated search for the expression patterns of SPARCL1 in relation to various clinicopathological features of BCa. We then carried out Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA). Furthermore, we investigated the correlations between SPARCL1 and immunological features, such as tumour mutation burden (TMB), immune activation processes, immune checkpoint expression, tumour immune dysfunction and exclusion (TIDE) scores, and chemotherapeutic sensitivity in BCa. Our analysis revealed that SPARCL1 was downregulated across multiple cancers. In BCa, elevated SPARCL1 was linked with advanced histopathologic stage, higher T and N stage, and poorer prognosis in the clinical cohort. In vitro experiments demonstrated that increased SPARCL1 expression inhibited cell proliferation, migration, and invasion. Additionally, highly expressed SPARCL1 was linked to elevated immune, stromal and ESTIMATE scores, as well as an increase in naive B cells, M2 macrophages, and resting mast cells. We observed a moderate correlation between SPARCL1 expression and CD163, VSIG4 and MS4A4A, which are markers of M2 macrophages. Furthermore, SPARCL1 expression was positively related to TMB, immune activation processes, TIDE scores, immune checkpoint expression, and chemotherapeutic sensitivity in BCa. Our study highlights the potential involvement of SPARCL1 in macrophage recruitment and polarization and suggests its utility as a biomarker for prognosis in BCa.
Insights
Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is downregulated in bladder cancer (BCa) and linked to poorer prognosis. Higher SPARCL1 inhibits BCa cell growth and correlates with immune responses, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a matricellular protein with understudied functions in bladder cancer (BCa).
- Understanding SPARCL1's role is crucial for identifying novel therapeutic targets and prognostic markers in BCa.
Purpose of the Study:
- To investigate the expression patterns and functional significance of SPARCL1 in bladder cancer.
- To explore the correlation between SPARCL1 and clinicopathological features, immune characteristics, and chemotherapeutic sensitivity in BCa.
Main Methods:
- Integrated analysis of SPARCL1 expression in relation to clinicopathological features.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Gene Set Enrichment Analysis (GSEA) to assess immune-related features, including tumor mutation burden (TMB), immune cell infiltration, and TIDE scores.
Main Results:
- SPARCL1 was found to be downregulated in multiple cancers, including BCa, where its elevated expression correlated with advanced stage and poorer prognosis.
- In vitro experiments showed that increased SPARCL1 inhibited BCa cell proliferation, migration, and invasion.
- High SPARCL1 expression was associated with increased immune and stromal scores, enhanced infiltration of naive B cells and M2 macrophages, and a positive correlation with TMB, immune activation, TIDE scores, immune checkpoints, and chemotherapeutic sensitivity.
Conclusions:
- SPARCL1 plays a role in regulating bladder cancer cell behavior and the tumor immune microenvironment, particularly in macrophage recruitment and polarization.
- SPARCL1 serves as a potential prognostic biomarker for bladder cancer, offering insights into treatment response and patient outcomes.
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