SMC3 Is Highly Expressed in Gliomas and Is Associated With Favorable Prognosis and B Cell–Related Immune Features

Introduction SMC3, a core component of the cohesin complex, plays diverse roles in tumorigenesis across different cancer types. However, its expression pattern, prognostic significance, and potential association with the immune microenvironment in gliomas remain largely unexplored. Methods In this retrospective study, we systematically analyzed SMC3 expression using multiple transcriptomic datasets, including CGGA (CGGA-325, CGGA-301), TCGA, and GEO (GSE4290, GSE50161), and validated protein-level expression in 44 clinical glioma specimens via immunohistochemistry. Associations with overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. Immune microenvironment features were evaluated using ESTIMATE and TIMER2.0, and pathway enrichment was analyzed through GSEA. Core B cell–related genes and signaling pathways associated with SMC3 were further identified by intersecting SMC3-correlated genes with MSigDB C7 and KEGG B cell receptor signaling gene sets. Results SMC3 was significantly overexpressed in glioma tissues compared with normal brain, with higher expression in lower-grade gliomas (LGG) than glioblastoma (GBM). High SMC3 expression was associated with prolonged OS across CGGA-325, CGGA-301, and the Validation Cohort, and remained prognostically favorable in specific clinical subgroups, including MGMT-unmethylated and 1p/19q non-codeleted tumors. SMC3 high-expression tumors exhibited lower overall immune and stromal scores but showed significant positive correlations with B cell and plasma cell infiltration. GSEA revealed enrichment of PI3K–AKT–MYC– and MTORC1-related pathways in high SMC3 tumors. Intersection analyses identified four core B cell–related genes (AKT3, CHUK, GSK3B, PIK3CA) within the PI3K–Akt signaling pathway, suggesting SMC3 expression may be associated with B cell–related immune features. Conclusions SMC3 is highly expressed in gliomas and is associated with favorable prognosis. Its expression correlates with B cell–related immune infiltration and activation of PI3K–Akt–MYC signaling, highlighting a potential role in shaping local immune microenvironments. These findings provide novel evidence for SMC3 as a prognostic biomarker and suggest a potential association with B cell–mediated immune features in gliomas.