Gong Xuantong, Gu Lishuang, Yang Di, He Yu, Li Qian, Qin Hao, Wang Yong
Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Ultrasound, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Elife. 2025 Jun 2;13:RP100923. doi: 10.7554/eLife.100923.
Triple-negative breast cancer (TNBC), an aggressive malignancy with limited tools to predict recurrence and drug sensitivity, exhibits ferroptotic heterogeneity across subtypes. However, the tumor microenvironment (TME) mediated by ferroptosis-related genes remains poorly characterized. This study integrates single-cell and bulk RNA sequencing data from the Gene Expression Omnibus to elucidate ferroptosis-driven TME features in TNBC, employing machine learning to develop prognostic and therapeutic response prediction models. At the single-cell level, T cells were classified into three subpopulations and macrophages into two subpopulations, with their infiltration degrees significantly correlated with clinical outcomes. A risk score model constructed based on these findings demonstrated robust predictive performance, validated in external cohorts with 3-, 4-, and 5-year area under the receiver operating characteristic curves of 0.65, 0.67, and 0.71, respectively. Notably, high-risk patients exhibited enhanced sensitivity to 27 therapeutic agents. By delineating ferroptosis-associated immune heterogeneity, this work provides a risk stratification tool to enhance prognostic precision and therapeutic decision-making in TNBC, while identifying genes offer actionable targets for TNBC precision medicine.
三阴性乳腺癌(TNBC)是一种侵袭性恶性肿瘤,预测复发和药物敏感性的工具有限,各亚型之间存在铁死亡异质性。然而,由铁死亡相关基因介导的肿瘤微环境(TME)的特征仍不清楚。本研究整合了来自基因表达综合数据库的单细胞和批量RNA测序数据,以阐明TNBC中由铁死亡驱动的TME特征,并利用机器学习开发预后和治疗反应预测模型。在单细胞水平上,T细胞被分为三个亚群,巨噬细胞被分为两个亚群,它们的浸润程度与临床结果显著相关。基于这些发现构建的风险评分模型显示出强大的预测性能,在外部队列中得到验证,3年、4年和5年的受试者工作特征曲线下面积分别为0.65、0.67和0.71。值得注意的是,高危患者对27种治疗药物表现出更高的敏感性。通过描绘与铁死亡相关的免疫异质性,这项工作提供了一种风险分层工具,以提高TNBC的预后准确性和治疗决策,同时识别出可为TNBC精准医学提供可操作靶点的基因。