The Oncogenic Functions of SPARCL1 in Bladder Cancer

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.