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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Guihua Hong,
  • Zhanyue Cui,
  • Xiaowen Xu,
  • Shiwei Lin,
  • Changqing Yang,
  • Ran Ding,
  • Ludan Liang,
  • Ying Chen,
  • Ziyue Tian

摘要

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.