S1P3 promotes low-grade glioma progression and affects tumor microenvironment infiltration

Abstract Background: Sphingosine-1-phosphate receptor 3 (S1P3) has been implicated in the progression of various tumors, but its role in low-grade glioma (LGG) remains unclear. This study investigates the impact of S1P3 expression on glioma progression, prognosis, and immune cell infiltration within the tumor microenvironment (TME). Methods: We analyzed clinicopathological and gene expression data from The Cancer Genome Atlas (TCGA) and performed univariate/multivariate Cox regression analyses to assess the prognostic value of S1P3 in LGG. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways associated with S1P3 expression. In vitro validation was performed using quantitative PCR, cell viability assays, wound healing assays, and Boyden chamber migration assays. Results: S1P3 overexpression was significantly associated with poor overall survival and molecular subtypes of LGG. GSEA revealed that S1P3 upregulation was linked to key oncogenic pathways, including DNA replication, cell cycle, MAPK, p53, and TGF-β signaling. Moreover, S1P3 expression correlated with increased infiltration of immune cells, including macrophages and T cells, as well as higher levels of immune checkpoint molecules. In vitro experiments confirmed that inhibiting S1P3 reduced glioma cell proliferation and migration. Conclusion: S1P3 serves as a potential prognostic biomarker in LGG and plays a critical role in TME immune cell infiltration. Understanding the S1P3-regulated pathways could provide new therapeutic targets for glioma treatment.