Bioinformatics reveal macrophages marker genes signature in breast cancer to predict prognosis

Breast cancer is a pivotal cause of global women cancer death. Immunotherapy has become a promising means to cure breast cancer. As constitutes of immune microenvironment of breast cancer, macrophages exert complicated functions in the tumour development and treatment. This study aims to develop a prognostic macrophage marker genes signature (MMGS). Single cell RNA sequence data analysis was performed to identify macrophage marker genes in breast cancer. TCGA database was used to construct MMGS model as a training cohort, and GSE96058 dataset was used to validate the MMGS as a validation cohort. Genes included in the MMGS model were: SERPINA1, CD74, STX11, ADAM9, CD24, NFKBIA, PGK1. MMGS risk score stratified by overall survival of patients divided them into high- and low-risk groups. And MMGS risk score remained independent prognostic factor in multivariate analysis after adjusting for classical clinical factors in both training and validation cohorts. Besides, hormone receptors negative and human epidermal growth factor receptor 2 (HER2) positive patients had higher risk score. MMGS showed better distinguishing capability between high-risk and low-risk groups in hormone receptor positive and HER2 negative subgroup. MMGS provides a new understanding of immune cell marker genes in breast cancer prognosis and may offer reference for immunotherapy decision for breast cancer patients.

乳腺癌是全球女性癌症相关死亡的核心诱因。免疫治疗已成为治疗乳腺癌极具潜力的手段。作为乳腺癌免疫微环境的组成成分，巨噬细胞在肿瘤发生发展与治疗过程中发挥着复杂多样的功能。本研究旨在构建一种预后性巨噬细胞标记基因特征（macrophage marker genes signature, MMGS）。本研究通过单细胞RNA测序（single cell RNA sequence）数据分析筛选乳腺癌相关巨噬细胞标记基因。以癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库作为训练集构建MMGS模型，并以GSE96058数据集作为验证集对该模型进行验证。该MMGS模型所包含的基因为：SERPINA1、CD74、STX11、ADAM9、CD24、NFKBIA、PGK1。基于患者总生存期的MMGS风险评分可将其划分为高风险组与低风险组。在训练集与验证集中，经校正经典临床因素后的多因素分析显示，MMGS风险评分仍为独立预后因素。此外，激素受体阴性及人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）阳性患者的风险评分更高。在激素受体阳性且HER2阴性的亚组中，MMGS对高低风险组的区分能力更为优异。MMGS为乳腺癌预后相关免疫细胞标记基因的研究提供了新视角，同时可为乳腺癌患者的免疫治疗决策提供参考依据。