PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■由于高发病率和死亡率，结肠腺癌（COAD）是一个严重的公共卫生问题。本研究旨在确定可能的肿瘤抗原和COAD的坏死亚型，以开发mRNA疫苗并选择合适的患者进行精确治疗。
■COAD的基因表达谱和临床信息来自癌症基因组图谱和基因表达综合，分别。我们使用cBioPortal全面研究了坏死相关基因（NRGs）的变化，并使用基因表达谱交互分析2筛选与COAD患者预后相关的中心NRGs。进行共识聚类分析以鉴定坏死亚型。使用加权基因共表达网络分析(WGCNA)来鉴定NRG的共表达模块。使用基于图形学习的降维方法评估了COAD的坏死景观。最后,对两种坏死亚型进行了药物敏感性分析.
■两种肿瘤抗原，根据BLC-2相关X蛋白（BAX）和白介素1β（IL1B）与患者预后和抗原呈递细胞浸润的关系，对其进行鉴定。在COAD患者中区分了两种坏死亚型（N1和N2），它们的特征在于它们的差异生存状态和免疫检查点蛋白和免疫遗传学细胞死亡调节剂的分子表达水平。此外，COAD的坏死景观表明，个体患者具有明显的异质性。使用WGCNA鉴定共表达模块，发现中心NRG参与各种免疫过程。药物敏感性分析表明，N1和N2亚型之间的药物敏感性存在显着差异。细胞实验表明，BAX和IL1B的过表达均促进COAD细胞的坏死，并增强CD8T细胞的细胞毒性。
■BAX和IL1B是开发抗COADmRNA疫苗的潜在抗原，特别适用于N2亚型患者。因此,这项研究将指导开发更有效的免疫治疗方法和确定合适的患者。
■COAD的基因表达谱和临床信息来自癌症基因组图谱和基因表达综合，分别。我们使用cBioPortal全面研究了坏死相关基因（NRGs）的变化，并使用基因表达谱交互分析2筛选与COAD患者预后相关的中心NRGs。进行共识聚类分析以鉴定坏死亚型。使用加权基因共表达网络分析(WGCNA)来鉴定NRG的共表达模块。使用基于图形学习的降维方法评估了COAD的坏死景观。最后,对两种坏死亚型进行了药物敏感性分析.
■两种肿瘤抗原，根据BLC-2相关X蛋白（BAX）和白介素1β（IL1B）与患者预后和抗原呈递细胞浸润的关系，对其进行鉴定。在COAD患者中区分了两种坏死亚型（N1和N2），它们的特征在于它们的差异生存状态和免疫检查点蛋白和免疫遗传学细胞死亡调节剂的分子表达水平。此外，COAD的坏死景观表明，个体患者具有明显的异质性。使用WGCNA鉴定共表达模块，发现中心NRG参与各种免疫过程。药物敏感性分析表明，N1和N2亚型之间的药物敏感性存在显着差异。细胞实验表明，BAX和IL1B的过表达均促进COAD细胞的坏死，并增强CD8T细胞的细胞毒性。
■BAX和IL1B是开发抗COADmRNA疫苗的潜在抗原，特别适用于N2亚型患者。因此,这项研究将指导开发更有效的免疫治疗方法和确定合适的患者。
