Discovery of an independent poor-prognosis subtype associated with tertiary lymphoid structures in breast cancer

作者：Ruiqi Liu, Xiaoqian Huang, Shiwei Yang, Wenbo Du, Xiaozhou Chen, Huamei Li · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1364506 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、IL-33, ST2, and ILC Pathways

Introduction: Tertiary lymphoid structures (TLSs) are ectopic lymphoid formations that arise in non-lymphoid tissues due to chronic inflammation. The pivotal function of TLSs in regulating tumor invasion and metastasis has been established across several cancers, such as lung cancer, liver cancer, and melanoma, with a positive correlation between increased TLS presence and improved prognosis. Nevertheless, the current research about the clinical significance of TLSs in breast cancer remains limited. Methods: In our investigation, we discovered TLS-critical genes that may impact the prognosis of breast cancer patients, and categorized breast cancer into three distinct subtypes based on critical gene expression profiles, each exhibiting substantial differences in prognosis (p = 0.0046, log-rank test), with Cluster 1 having the best prognosis, followed by Cluster 2, and Cluster 3 having the worst prognosis. We explored the impact of the heterogeneity of these subtypes on patient prognosis, the differences in the molecular mechanism, and their responses to drug therapy and immunotherapy. In addition, we designed a machine learning-based classification model, unveiling highly consistent prognostic distinctions in several externally independent cohorts. Results: A notable marker gene CXCL13 was identified in Cluster 3, potentially pivotal in enhancing patient prognosis. At the single-cell resolution, we delved into the adverse prognosis of Cluster 3, observing an enhanced interacti...