PSMC3IP as a prognostic biomarker and immunomodulatory regulator in low-grade glioma: insights from multi-omics and methylation analysis

PSMC3IP, a gene involved in proteasome function, has been linked to various cancers, though its role in low-grade glioma (LGG) remains underexplored. This study investigates its expression and mechanisms in LGG, offering insights into treatment and prognosis evaluation. Integrate multi-omics data from TCGA, CGGA, and other sources to analyze the association between PSMC3IP expression and clinical features and survival prognosis, and combine methylation analysis, immune infiltration assessment, and GSEA-enriched pathways to elucidate its functional mechanisms. The overexpression of PSMC3IP in LGG was significantly correlated with malignant clinical features, including higher WHO grade, tumor recurrence, and 1p19q co-deletion (<i>p</i> &lt; 0.05). Patients with high PSMC3IP expression exhibited significantly shortened overall survival (<i>p</i> &lt; 0.001). Methylation analysis revealed that the cg12628062 locus negatively regulated PSMC3IP expression (<i>r</i> = –0.22, <i>p</i> &lt; 0.001). Immune microenvironment profiling demonstrated that PSMC3IP overexpression promoted tumor associated macrophages to polarize towards M2 morphology, suppressed CD8+ T cell activity, and elevated expression of immune checkpoints (PDCD1/CTLA-4). Gene Set Enrichment Analysis (GSEA) further highlighted its enrichment in DNA replication and base excision repair pathways, suggesting its oncogenic role through genomic instability and immunomodulatory mechanisms. PSMC3IP is overexpressed in LGG and serves as an independent prognostic factor for poor survival. Its involvement in immune regulation and key molecular pathways, including DNA replication, suggests it may be a target for therapeutic strategies in LGG.