Jinan University, Guangzhou, China.
Department of Gynecology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, China.
Medicine (Baltimore). 2023 Aug 4;102(31):e34571. doi: 10.1097/MD.0000000000034571.
Immunogenic cell death (ICD) is a unique phenomenon that can trigger comprehensive, adaptive immune responses through damage-associated molecular patterns, offering a promising avenue for tumor immunotherapy. However, the role of ICD-related genes and their correlation with endometrial carcinoma (EC), the most prevalent gynecologic malignancy, remains unclear. This study examined genetic, transcriptional, and clinical data of EC obtained from the Cancer Genome Atlas database. Unsupervised clustering analysis was utilized to identify distinct ICD clusters based on the expression of ICD-related genes. Regarding the different clusters, their survival analysis, assessment of the immune microenvironment, immune cell infiltration, immune checkpoint analysis, and tumor mutation burden analysis were performed. Furthermore, an ICD risk signature was established using univariate Cox regression and least absolute shrinkage and selection operator analysis. The Chi-square test was employed to investigate the relationship between the ICD score and clinical features. Multiple computational analytical tools were used to assess immune annotation, somatic mutations, tumor mutation burden, and response to immunotherapy and chemotherapy drugs in different ICD score groups. Two ICD clusters were identified, indicating that the ICD-high cluster was associated with improved prognosis, abundant immune cell infiltration, and enrichment of pathways related to immunologic activation. Moreover, the ICD risk signature showed predictive value for the immune microenvironment, immunotherapy response, chemotherapy susceptibility, and prognosis in EC. Our findings offer novel insights into personalized treatment strategies for EC patients.
免疫原性细胞死亡（ICD）是一种独特的现象，它可以通过损伤相关分子模式触发全面的适应性免疫反应，为肿瘤免疫治疗提供了有前途的途径。然而，ICD 相关基因的作用及其与子宫内膜癌（EC）的相关性，EC 是最常见的妇科恶性肿瘤，仍不清楚。本研究检查了从癌症基因组图谱数据库获得的 EC 的遗传、转录和临床数据。利用无监督聚类分析，根据 ICD 相关基因的表达，确定了不同的 ICD 聚类。对于不同的聚类，进行了它们的生存分析、免疫微环境评估、免疫细胞浸润、免疫检查点分析和肿瘤突变负荷分析。此外，使用单变量 Cox 回归和最小绝对收缩和选择算子分析建立了 ICD 风险特征。卡方检验用于研究 ICD 评分与临床特征之间的关系。使用多种计算分析工具评估不同 ICD 评分组的免疫注释、体细胞突变、肿瘤突变负荷以及对免疫治疗和化疗药物的反应。确定了两个 ICD 聚类，表明 ICD-高聚类与改善的预后、丰富的免疫细胞浸润以及与免疫激活相关的途径富集有关。此外，ICD 风险特征显示了对 EC 中免疫微环境、免疫治疗反应、化疗敏感性和预后的预测价值。我们的研究结果为 EC 患者的个性化治疗策略提供了新的见解。
