FGD3 as a prognostic and immunological biomarker: a pan-cancer analysis of its role in tumor progression and the immune landscape

Background FGD3 , a member of the FGD family, regulates GTPase activity and cellular morphology, thereby influencing tumor proliferation and migration. However, its role across diverse cancer types remains insufficiently understood. Methods Using TCGA and GTEx databases, FGD3 expression was compared between tumor and normal tissues to assess its relevance to cancer. Single-cell transcriptomic data from TISCH were used to characterize FGD3 expression across immune cell subsets. Univariate Cox regression was performed to evaluate associations between FGD3 expression and patient survival. TIMER2.0 Spearman correlation analysis examined its relationship with immune cell infiltration. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) revealed FGD3 ’s association with immune and metabolic pathways. Bioinformatics and molecular docking predicted interactions with anticancer drugs. Experimental validation demonstrated that FGD3 knockdown suppresses cancer cell migration and proliferation, indicating an anti-tumor role in breast cancer. Results FGD3 expression varies across tumors, with differing prognostic implications. In most malignancies, expression inversely correlates with copy number variation (CNV) and methylation and associates with immunotherapy biomarkers and responses. ESTIMATE and immune infiltration analyses suggest a role in immunosuppression and tumor immunity. Experimental downregulation of FGD3 significantly reduces cell proliferation and migration, highlighting its therapeutic potential. Conclusion FGD3 plays an important role in tumorigenesis and progression and may serve as a promising biomarker for cancer prognosis. Its expression is inversely associated with tumor metastasis. Experimental findings further suggest that FGD3 may function as a migration-suppressive factor in breast cancer. Collectively, these results provide new insights into the biological role of FGD3 and suggest its potential as a therapeutic target.