Regulatory patterns of antibody-dependent cellular phagocytosis-related genes in triple-negative breast cancer: An integrated multi-omics and single-cell analysis.

Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to aggressive biology and limited targeted therapies. While antibody-dependent cellular phagocytosis (ADCP) offers potential for immune intervention, its molecular drivers and clinical implications in TNBC are poorly defined. Multi-omics analysis of TNBC specimens (TCGA, METABRIC, GEO) integrated differential expression, protein-protein interactions, single-cell RNA sequencing (scRNA-seq), and drug sensitivity profiling. Prognostic models were validated across three cohorts. We identified six core ADCP regulators (MUC1, PTEN, BCL6, CD19, LCK, CD79B) defining a high-risk subgroup with elevated metastasis risk and reduced 5-year DFS. scRNA-seq revealed subtype-specific expression patterns across 100,064 cells, linking MUC1/BCL6 to macrophage phagocytosis suppression. A prognostic nomogram integrating these genes achieved superior accuracy versus clinical staging, validated externally. High-risk tumors exhibited PARP inhibitor sensitivity but CDK4/6 inhibitor resistance. This study establishes ADCP-related genes as dual biomarkers for TNBC risk stratification and therapy selection, revealing actionable vulnerabilities for precision phagocytosis modulation.