Department of General Surgery, Panjin Liao-Oil Field Gem Flower Hospital, Panjin, 124000, China.
Department of Rheumatology and Immunology, Panjin Liao-Oil Field Gem Flower Hospital, Panjin, 124000, China.
Sci Rep. 2024 Jan 23;14(1):2025. doi: 10.1038/s41598-024-52353-4.
Lack of specific biomarkers and effective drug targets constrains therapeutic research in breast cancer (BC). In this regard, therapeutic modulation of damage-associated molecular patterns (DAMPs)-induced immunogenic cell death (ICD) may help improve the effect of immunotherapy in individuals with BC. The aim of this investigation was to develop biomarkers for ICD and to construct ICD-related risk estimation models to predict prognosis and immunotherapy outcomes of BC. RNA-seq transcriptome information and medical data from individuals with BC (n = 943) were obtained from TCGA. Expression data from a separate BC cohort (GEO: GSE20685) were used for validation. We identified subtypes of high and low ICD gene expression by consensus clustering and assessed the connection between ICD subtypes and tumor microenvironment (TME). In addition, different algorithms were used to construct ICD-based prognostic models of BC. BC samples were categorized into subtypes of high and low ICD expression depending on the expression of genes correlated with ICD. The subtype of ICD high-expression subtypes are correlated with poor prognosis in breast cancer, while ICD low-expression subtypes may predict better clinical outcomes. We also created and verified a predictive signature model depending on four ICD-related genes (ATG5, CD8A, CD8B, and HSP90AA1), which correlates with TME status and predicts clinical outcomes of BC patients. We highlight the connection of ICD subtypes with the dynamic evolution of TME in BC and present a novel ICD-based prognostic model of BC. In clinical practice, distinction of ICD subtype and assessment of ICD-related biomarkers should help guide treatment planning and improve the effectiveness of tumor immunotherapy.
缺乏特异性生物标志物和有效的药物靶点限制了乳腺癌 (BC) 的治疗研究。在这方面,损伤相关分子模式 (DAMPs) 诱导的免疫原性细胞死亡 (ICD) 的治疗调节可能有助于提高 BC 患者免疫治疗的效果。本研究旨在开发 ICD 的生物标志物,并构建 ICD 相关风险评估模型,以预测 BC 的预后和免疫治疗结果。从 TCGA 获得了 943 名 BC 患者的 RNA-seq 转录组信息和医学数据。来自单独的 BC 队列 (GEO: GSE20685) 的表达数据用于验证。我们通过共识聚类识别出高和低 ICD 基因表达的亚型,并评估了 ICD 亚型与肿瘤微环境 (TME) 之间的关系。此外,还使用不同的算法构建了基于 ICD 的 BC 预后模型。BC 样本根据与 ICD 相关的基因的表达分为高和低 ICD 表达亚型。ICD 高表达亚型与乳腺癌预后不良相关,而 ICD 低表达亚型可能预示着更好的临床结局。我们还根据四个与 ICD 相关的基因 (ATG5、CD8A、CD8B 和 HSP90AA1) 创建并验证了一个预测签名模型,该模型与 TME 状态相关,并预测了 BC 患者的临床结局。我们强调了 ICD 亚型与 BC 中 TME 动态演变的关系,并提出了一种新的基于 ICD 的 BC 预后模型。在临床实践中,区分 ICD 亚型和评估 ICD 相关生物标志物应有助于指导治疗计划并提高肿瘤免疫治疗的效果。
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