Abstract
BACKGROUND: guanosine diphosphate dissociation inhibitor 1 (GDI1), a key regulator of small GTPase activity, plays a critical role in cellular signal transduction and is closely associated with the development and progression of various cancers. However, its specific functional mechanisms in breast cancer (BRCA) remain to be further elucidated. METHODS: In this study, we analyzed the differential expression of GDI1 based on the The Cancer Genome Atlas-BRCA and Gene Expression Omnibus databases, and validated its expression levels using the HPA database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, along with gene set enrichment analysis (GSEA), were employed to elucidate its potential biological functions. The prognostic value of GDI1 was evaluated through Cox regression and Kaplan-Meier survival curves, and a prognostic nomogram with calibration curves was constructed. Protein-protein interaction network analysis was utilized to identify key interacting genes, and their roles were further explored through correlation analysis and GO/KEGG analysis of hub genes. GSEA was performed to assess immune infiltration levels, while the methylation status of GDI1 was analyzed using the UALCAN and MethSurv databases. Additionally, the mutation frequency and somatic copy number alterations (SCNA) of GDI1 were investigated. RESULTS: The expression of GDI1 was significantly higher in BRCA tissues compared to normal tissues. Patients with low GDI1 expression exhibited markedly longer OS than those with high expression. Both univariate and multivariate Cox regression analyses confirmed that high GDI1 expression is an independent prognostic factor for OS in BRCA patients. GDI1 expression showed a negative correlation with the infiltration levels of B cells, macrophages, dendritic cells, and Th1 cells. Patients with low GDI1 methylation had significantly worse OS than those with BRCA alteration types, including arm-level deletions, diploid/normal, and arm-level gains. CONCLUSIONS: GDI1 is highly expressed in BRCA and is significantly associated with poor patient prognosis. Its expression level influences the tumor immune microenvironment, and low methylation status indicates worse clinical outcomes. These findings suggest that GDI1 may serve as a potential biomarker for prognosis assessment and immune regulation in BRCA, providing new directions for targeted therapy.