Abstract
BACKGROUND: The tumor microenvironment (TME) of breast cancer (BRCA) influences disease progression through dynamic interactions between immunity and stroma, but its key regulatory molecules and prognostic value remain to be elucidated. The aim of this study was to explore the prognostic potential of immunoglobulin λ-like polypeptide 5 (IGLL5) in BRCA and its association with immune infiltration in TME. METHODS: 1178 BRCA cases were obtained from The Cancer Genome Atlas (TCGA) database. CIBERSORT and ESTIMATE computational methods were used to quantify the composition of tumor-infiltrating immune cells (TICs) and the presence of immune and stromal components. Prognostic indicator closely associated with BRCA was identified by Cox regression analysis and protein-protein interaction (PPI) network construction. Through Gene Set Enrichment Analysis (GSEA) and other means, the correlations between IGLL5 expression and patient survival, immune activities, metabolic pathways, and immune cell types were studied. RESULTS: Overall survival was significantly prolonged in patients with high IGLL5 expression (HR=0.62, 95% CI 0.45-0.86, P=0.013) and positively correlated with immune-activating pathways (complement signaling, interferon response) and anti-tumor TICs (CD8(+) T cells, M1 macrophages) (r>0.3, P<0.001) and negatively correlated with tumor-promoting TICs (M2 macrophages, resting NK cells). The low IGLL5 group was enriched in metabolic pathways (estrogen response, oxidative phosphorylation), suggesting that it may promote immune escape through metabolic reprogramming. CONCLUSION: IGLL5 is a novel prognostic marker for BRCA, and its expression level affects patient survival by modulating TME immune infiltration and metabolic reprogramming. This study provides a theoretical basis for IGLL5-directed immunotherapeutic strategies (e.g., combining PD-1 inhibitors), and its mechanism needs to be verified by multicenter clinical cohorts and functional experiments in the future.