Lu Dezhi, Qiu Sifang, Zeng Zhiqiang
Department of Breast, Foshan Fosun Chancheng Hospital, Foshan, Guangdong Province, China.
Department of Gastroenterology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
Discov Oncol. 2025 Jan 10;16(1):31. doi: 10.1007/s12672-025-01770-6.
Growing evidence has demonstrated the association between necroptosis and tumorigenesis and immunotherapy. However, the influence of overall necroptosis related genes on prognosis and immune microenvironment of breast cancer is still unclear. In this study, We systematically analyzed the necroptosis related gene patterns and tumor microenvironment characteristics of 1294 breast cancer patients by clustering the gene expression of 22 necroptosis related genes. Three breast cancer subtypes that had different necroptosis patterns and distinct tumor microenvironment characteristics were recognized. The NecroptosisCluster B was featured by favorable prognosis, activated immune molecules and higher scores of immune cells. The NecroptosisScore was constructed to quantitatively evaluate the necroptosis level of individual patients. High NecroptosisScore were characterized by elevated expression levels of MHC molecules, stimulated infiltration of immune cells and lengthened survival. High NecroptosisScore were correlated with lower tumor mutation burden (TMB), and higher PD-1/CTLA4 expression. Surprisingly, patients with high NecroptosisScore exhibited better benefits in immunotherapy. This study highlighted that necroptosis was correlated with several aspects of breast cancer and affected the immune function. Further understanding of necroptosis will support our insight into the tumor immune landscape of breast cancer and facilitate the development of more effective treatment strategies.
越来越多的证据表明坏死性凋亡与肿瘤发生及免疫治疗之间存在关联。然而，整体坏死性凋亡相关基因对乳腺癌预后和免疫微环境的影响仍不清楚。在本研究中，我们通过对22个坏死性凋亡相关基因的表达进行聚类分析，系统地分析了1294例乳腺癌患者的坏死性凋亡相关基因模式和肿瘤微环境特征。识别出了三种具有不同坏死性凋亡模式和独特肿瘤微环境特征的乳腺癌亚型。坏死性凋亡聚类B的特征是预后良好、免疫分子激活以及免疫细胞评分较高。构建了坏死性凋亡评分以定量评估个体患者的坏死性凋亡水平。高坏死性凋亡评分的特征是MHC分子表达水平升高、免疫细胞浸润受刺激以及生存期延长。高坏死性凋亡评分与较低的肿瘤突变负荷（TMB）以及较高的PD-1/CTLA4表达相关。令人惊讶的是，高坏死性凋亡评分的患者在免疫治疗中表现出更好的疗效。本研究强调坏死性凋亡与乳腺癌的多个方面相关，并影响免疫功能。对坏死性凋亡的进一步了解将有助于我们洞察乳腺癌的肿瘤免疫格局，并促进更有效治疗策略的开发。
