结肠腺癌（COAD）因其高发病率和死亡率而成为严重的公共卫生问题。本研究旨在鉴定 COAD 可能的肿瘤抗原和坏死性凋亡亚型，用于开发 mRNA 疫苗和选择合适的患者进行精准治疗。 COAD 的基因表达谱和临床信息分别来自癌症基因组图谱和基因表达综合数据库。我们利用cBioPortal全面研究了坏死性凋亡相关基因（NRG）的变化，并利用基因表达谱交互分析2筛选了与COAD患者预后相关的中枢NRG。通过共识聚类分析来识别坏死性凋亡亚型。加权基因共表达网络分析（WGCNA）用于识别 NRG 的共表达模块。使用基于图学习的降维方法评估 COAD 的坏死性凋亡景观。最后，对两种坏死性凋亡亚型进行了药物敏感性分析。根据两种肿瘤抗原BLC-2相关X蛋白（BAX）和白细胞介素1β（IL1B）与患者预后和抗原呈递细胞浸润的关系，确定了它们。 COAD 患者有两种坏死性凋亡亚型（N1 和 N2），其特征在于不同的生存状态以及免疫检查点蛋白和免疫遗传细胞死亡调节剂的分子表达水平。此外，COAD 的坏死性凋亡情况表明个体患者具有明显的异质性。使用 WGCNA 鉴定了共表达模块，并且发现中枢 NRG 参与各种免疫过程。药物敏感性分析表明N1和N2亚型之间药物敏感性存在显着差异。细胞实验表明，BAX和IL1B的过表达都会促进COAD细胞的坏死性凋亡，并增强CD8 T细胞的细胞毒性。BAX和IL1B是开发抗COAD mRNA疫苗的潜在抗原，特别是针对N2亚型患者。因此，这项研究将指导更有效的免疫治疗方法的开发和合适患者的识别。© 2024 作者。由爱思唯尔有限公司出版

Colon adenocarcinoma (COAD) is a serious public health issue due to high incidence and mortality rate. This study aimed to identify possible tumor antigens and necroptosis subtypes of COAD for the development of mRNA vaccines and the selection of appropriate patients for precision therapy.Gene expression profiles and clinical information for COAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. We comprehensively studied the alterations in necroptosis-related genes (NRGs) using cBioPortal, and screened the hub NRGs associated with the prognosis of patients with COAD using Gene Expression Profiling Interactive Analysis 2. Consensuses clustering analysis was performed to identify necroptosis subtypes. Weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of the NRGs. The necroptosis landscape of COAD was assessed using graph learning-based dimensionality reduction. Finally, a drug sensitivity analysis of the two necroptosis subtypes was performed.Two tumor antigens, BLC-2-associated X protein (BAX) and interleukin 1 beta (IL1B) were identified based on their associations with prognosis of patients and antigen presenting cell infiltration. Two necroptosis subtypes (N1 and N2) were distinguished in patients with COAD, and they were characterized by their differential survival status and molecular expression levels of immune checkpoint proteins and immunogenetic cell death modulators. Furthermore, the necroptosis landscape of COAD indicated that individual patients had obvious heterogeneity. Co-expression modules were identified using WGCNA, and the hub NRGs were found to be involved in various immune processes. Drug sensitivity analysis indicated that there were significant differences in drug sensitivity between the N1 and N2 subtypes. Cell experiments suggested that both overexpression of BAX and IL1B promoted necroptosis of COAD cells and enhanced the cytotoxicity of CD8+ T cells.BAX and IL1B are potential antigens for the development of anti-COAD mRNA vaccines, specifically for patients with the N2 subtype. Consequently, this study will guide the development of more effective immunotherapeutic approaches and the identification of appropriate patients.© 2024 The Authors. Published by Elsevier Ltd.