Xu Ming, Lu Jin-Hua, Zhong Ya-Zhen, Jiang Jing, Shen Yue-Zhong, Su Jing-Yang, Lin Sheng-You
Department of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Zhejiang, China.
Department of Traditional Chinese Medicine, The First People's Hospital of Tongxiang, Zhejiang, China.
Front Oncol. 2022 Apr 4;12:870914. doi: 10.3389/fonc.2022.870914. eCollection 2022.
Triple-negative breast cancer (TNBC) is defined as a highly aggressive type of breast cancer which lacks specific biomarkers and drug targets. Damage-associated molecular pattern (DAMP)-induced immunogenic cell death (ICD) may influence the outcome of immunotherapy for TNBC patients. This study aims to develop a DAMPs gene signature to classify TNBC patients and to further predict their prognosis and immunotherapy outcome.
We identified the DAMPs-associated subtypes of 330 TNBCs using K-means analysis. Differences in immune status, genomic alterations, and predicted immunotherapy outcome were compared among each subtype.
A total of 330 TNBCs were divided into three subtypes according to DAMPs gene expression: the nuclear DAMPs subtype, featuring the upregulation of nuclear DAMPs; the inflammatory DAMPs subtype, characterized by the gene set enrichment of the adaptive immune system and cytokine signaling in the immune system; and the DAMPs-suppressed subtype, having the lowest level of ICD-associated DAMPs. Among them, the inflammatory subtype patients had the most favorable survival, while the DAMPs-suppressed subtype was associated with the worst prognosis. The DAMPs subtyping system was successfully validated in the TCGA cohort. Furthermore, we systemically revealed the genomic alterations among the three DAMPs subtypes. The inflammatory DAMPs subtype was predicted to have the highest response rate to immunotherapy, suggesting that the constructed DAMPs clustering had potential for immunotherapy efficacy prediction.
We established a novel ICD-associated DAMPs subtyping system in TNBC, and DAMPs expression might be a valuable biomarker for immunotherapy strategies. Our work could be helpful to the development of new immunomodulators and may contribute to the development of precision immunotherapy for TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性很强的乳腺癌类型，缺乏特异性生物标志物和药物靶点。损伤相关分子模式（DAMP）诱导的免疫原性细胞死亡（ICD）可能影响TNBC患者的免疫治疗结果。本研究旨在开发一种DAMPs基因特征，用于对TNBC患者进行分类，并进一步预测其预后和免疫治疗结果。
我们使用K均值分析确定了330例TNBC的DAMPs相关亚型。比较了各亚型之间免疫状态、基因组改变和预测的免疫治疗结果的差异。
根据DAMPs基因表达，330例TNBC共分为三个亚型：核DAMPs亚型，其特征是核DAMPs上调；炎症性DAMPs亚型，其特征是适应性免疫系统和免疫系统中细胞因子信号的基因集富集；以及DAMPs抑制亚型，其ICD相关DAMPs水平最低。其中，炎症亚型患者的生存率最有利，而DAMPs抑制亚型与最差的预后相关。DAMPs分型系统在TCGA队列中得到成功验证。此外，我们系统地揭示了三种DAMPs亚型之间的基因组改变。炎症性DAMPs亚型预计对免疫治疗的反应率最高，这表明构建的DAMPs聚类具有预测免疫治疗疗效的潜力。
我们在TNBC中建立了一种新的与ICD相关的DAMPs分型系统，DAMPs表达可能是免疫治疗策略的一个有价值的生物标志物。我们的工作可能有助于开发新的免疫调节剂，并可能有助于TNBC精准免疫治疗的发展。
