研究动态
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通过生物信息学分析,鉴定与预测子宫内膜癌患者存活和免疫疗法相关的免疫原性细胞死亡亚型。

Identification of immunogenic cell death-related subtypes used for predicting survival and immunotherapy of endometrial carcinoma through a bioinformatics analysis.

发表日期:2023 Aug 04
作者: Zhen Liu, Yongjin Luo, Linhong Su, Xiaoxia Hu
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

免疫原性细胞死亡(ICD)是一种独特的现象,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景的途径。然而,与子宫内膜癌(EC)这种最常见的妇科恶性肿瘤相关的ICD相关基因的作用仍不清楚。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相关基因的表达识别出不同的ICD聚类。关于不同的聚类,进行了生存分析,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风险签名。采用卡方检验研究了ICD得分与临床特征之间的关系。使用多种计算分析工具评估了不同ICD得分组的免疫注释,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。鉴定了两个ICD聚类,表明ICD高聚类与良好预后,丰富的免疫细胞浸润以及与免疫激活相关的通路富集有关。此外,ICD风险签名在EC的免疫微环境,免疫治疗反应,化疗敏感性和预后方面具有预测价值。我们的发现为EC患者个体化治疗策略提供了新的见解。版权所有 © 2023作者。由 Wolters Kluwer Health, Inc. 发布。
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.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.