乳腺癌（BC）是全球女性最常见的恶性肿瘤之一。本研究旨在开发基于吞噬相关基因（ARG）的预后特征。 BC 患者的转录组和临床数据是从癌症基因组图谱和 GEO 数据库下载的。采用差异表达分析、单变量 Cox 比例风险回归和最小绝对收缩和选择算子 Cox 回归来构建预后特征。进行了共识聚类、免疫浸润和药物敏感性评估、基因集富集分析以及列线图的开发。使用癌细胞系百科全书和临床样本的数据验证了 ARG 的表达。 11 个 ARG 在 BC 中异常表达，其中 5 个与 BC 预后显着相关。共识聚类确定了两种具有不同预后的分子亚型。开发了包括 5 个 ARG（VIM、TUBB1、TUBA3E、TUBA3D、TUBA1C）的预后特征，在预测 BC 预后方面表现出高性能。低风险组表现出细胞外基质组织和细胞迁移过程的富集，同时染色体分离受到抑制。此外，该组患者还表现出多种信号通路的激活，包括 MAPK、PI3K-AKT 和 cAMP 通路，而细胞周期和中性粒细胞胞外陷阱的形成则显着受到抑制。该特征还与免疫浸润和药物敏感性相关。构建了包含风险特征、临床分期和化疗的列线图，在预测预后方面表现出优异的性能。特征相关基因的表达在 BC 患者中得到了验证。这项研究成功构建了 BC 中基于 ARG 的分子亚型和预后特征，并开发了列线图。作者版权所有 © 2024。由 Wolters Kluwer Health, Inc. 出版

Breast cancer (BC) is 1 of the most common malignant tumors among women globally. This study aimed to develop a prognostic signature based on aggrephagy-related genes (ARGs). Transcriptomic and clinical data for BC patients were downloaded from the cancer genome atlas and GEO databases. Differential expression analysis, univariate Cox proportional hazards regression and least absolute shrinkage and selection operator Cox regression were employed to construct a prognostic signature. Consensus clustering, evaluation of immune infiltration and drug sensitivity, and gene set enrichment analysis, and development of nomogram were performed. The expression of ARGs was validated using data from the Cancer Cell Line Encyclopedia and clinical samples. Eleven ARGs were abnormally expressed in BC, with 5 showing significant correlations with BC prognosis. Consensus clustering identified 2 molecular subtypes with distinct prognoses. A prognostic signature including 5 ARGs (VIM, TUBB1, TUBA3E, TUBA3D, TUBA1C) was developed, which showed high performance in predicting BC prognosis. The low-risk group showed enrichment in extracellular matrix organization and cell migration processes while chromosome separation was suppressed. Additionally, patients in this group also show activation in several signaling pathways including MAPK, PI3K-AKT, and cAMP pathways, whereas cell cycle and neutrophil extracellular trap formation were significantly inhibited. The signature was also associated with immune infiltration and drug sensitivity. A nomogram incorporating the risk signature, clinical stage and chemotherapy was constructed, demonstrating excellent performance in predicting prognosis. The expression of signature-related genes were validated in patients with BC. This study successfully constructed molecular subtypes and a prognostic signature based on ARGs in BC, and developed a nomogram.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.