Syntaphilin inhibits glioma invasion via modulating mitochondria redistribution and shapes the immune microenvironment: A potential prognostic biomarker

BACKGROUND: Glioma remains a lethal brain malignancy with a dismal prognosis. Syntaphilin (SNPH), a mitochondrial anchoring protein, shows emerging relevance in cancer biology. This study investigates the diagnostic and prognostic potential of SNPH, while elucidatingits functional mechanisms in glioma progression. METHODS: The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas (HPA) were utilized to systematically analyze SNPH, including its differential transcriptional and translational expression, survival correlation, functional enrichment, and immune microenvironment in glioma. Subsequently, the effects of SNPH on cell migration, invasion, mitochondria distribution, epithelial-mesenchymal transition, focal adhesion (FA) maturation and FA kinase (FAK) signaling were validated via in vitro. RESULTS: SNPH expression was markedlydownregulatedin glioma (P < 0.001), demonstratinghigh diagnostic potential for glioma detection (area under the curve = 0.819). Clinically, decreasedSNPH levelswere associatedwith aggressive features(WHO grade G4, glioblastoma subtype) (both P < 0.001), unfavorable molecular characteristics[IDH-wildtype (P = 0.005), 1p19q non-codeletion (P < 0.001)], and significantlypredicted worse overall survival (P < 0.001). Functional enrichment analyses revealed SNPH's involvementin immunomodulation and migration-related processes, particularly FA pathway and FAK signaling. Immune profiling indicated an inverse correlation between SNPH expression and the abundance of T helper cells, macrophages and neutrophils. In vitro, SNPH overexpression suppressed invasion and epithelial-mesenchymal transition. Mechanistically, it promoted perinuclear mitochondrial clustering, attenuated FA maturation, FAK phosphorylation and RhoA/Rac1/Cdc42 expression. CONCLUSION: These findings establish SNPH as a novel diagnostic/prognostic biomarker and metastasis suppressor in glioma, functioning through mitochondrial repositioning-mediated inhibition of migration pathways.