Jiang Xiwei, Zhang Jinqing, Liu Xiaoming
Department of Thyroid and Breast Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, 250031, China.
Sci Rep. 2025 May 29;15(1):18916. doi: 10.1038/s41598-025-03825-8.
Antibody-dependent cellular phagocytosis (ADCP) has potential in breast cancer (BRCA) treatment, but the prognostic significance of ADCP-associated regulators (PRs) in BRCA remains unclear, necessitating this study. Firstly, candidate genes were identified by crossing differentially expressed genes (DEGs) with PRs, and prognostic genes were selected from these. A risk model based on SIAH2 and PIGR was constructed and validated in the GSE42568 cohort. We also assessed the relationship between expression of prognostic genes and clinical characteristics. From these, independent prognostic factors were selected and a nomogram was constructed to predict survival in BRCA patients. Immune microenvironment analysis revealed that PIGR had the strongest positive correlation with naive B cells, while SIAH2 showed the strongest negative correlation with activated memory CD4 T cells. Moreover, drug sensitivity analysis revealed that 109 drugs differed between high- and low-risk groups. Meanwhile, single-cell analysis identified epithelial cells (EPCs) as key cells, with PIGR highly expressed in the middle stage and SIAH2 in the early stage of cell differentiation. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the up-regulation of SIAH2 and down-regulation of PIGR in BRCA. These findings suggest that SIAH2 and PIGR are potential prognostic genes and novel therapeutic targets for BRCA management.
抗体依赖性细胞吞噬作用（ADCP）在乳腺癌（BRCA）治疗中具有潜力，但ADCP相关调节因子（PRs）在BRCA中的预后意义仍不清楚，因此有必要进行本研究。首先，通过将差异表达基因（DEGs）与PRs交叉来鉴定候选基因，并从这些基因中选择预后基因。构建了基于SIAH2和PIGR的风险模型，并在GSE42568队列中进行了验证。我们还评估了预后基因表达与临床特征之间的关系。从中选择独立的预后因素并构建列线图以预测BRCA患者的生存率。免疫微环境分析显示，PIGR与初始B细胞的正相关性最强，而SIAH2与活化记忆CD4 T细胞的负相关性最强。此外，药物敏感性分析显示，高风险组和低风险组之间有109种药物存在差异。同时，单细胞分析确定上皮细胞（EPCs）为关键细胞，PIGR在细胞分化中期高表达，SIAH2在早期高表达。最后，逆转录定量聚合酶链反应（RT-qPCR）证实了BRCA中SIAH2的上调和PIGR的下调。这些发现表明，SIAH2和PIGR是BRCA管理的潜在预后基因和新型治疗靶点。
