Li Yunlong, Jiang Xunliang, Cao Hui, Wu Xiao, Zhang Huimin, Ma Hongjiang, Wang Liangbo, Kang Boyu, Xie Mianjiao, Li Shisen
Department of Gastrointestinal Surgery, The First Affiliated Hospital of the Military Medical University of the PLA Air Force, Xian, China.
Department of Experimental Surgery, The First Affiliated Hospital of the Military Medical University of the PLA Air Force, Xian, China.
IUBMB Life. 2025 Mar;77(3):e70009. doi: 10.1002/iub.70009.
The cGAS-STING signaling pathway has emerged as a critical player in the immune response against cancer, including colorectal adenocarcinoma (COAD). Understanding the impact of this pathway on COAD at multiple omics levels is crucial for advancing cancer immunotherapy and precision medicine. This study aimed to investigate the relationship between cGAS-STING-related genes and COAD, analyzing gene mutations, copy number variations, DNA methylation, and gene expression to uncover the pathway's influence on COAD prognosis. Utilizing multi-omics sequencing data from TCGA and GEO databases, key core genes in the cGAS-STING pathway were identified and further validated through PCR and Western blot analysis. Mutations and copy number variations in the CASP8 and RIPK1 genes, differential DNA methylation patterns, and mRNA expression levels of specific genes were assessed to determine their impact on COAD prognosis. Validation through tissue samples highlighted NLRC3, CASP1, AIM2, and CXCL10 as core genes in the cGAS-STING pathway. Our findings demonstrate that mutations and copy number variations in CASP8 and RIPK1, differential DNA methylation patterns, and altered gene expression levels significantly influence the prognosis of COAD. The identification of core genes in the cGAS-STING pathway, particularly NLRC3, CASP1, AIM2, and CXCL10, has led to the development of a prognostic model predicting poor tumor outcomes through immune cell infiltration. This study provides valuable insights into the mechanisms of the cGAS-STING pathway in COAD and offers potential directions for future research in cancer immunotherapy and precision medicine.
cGAS-STING信号通路已成为包括结直肠癌（COAD）在内的癌症免疫反应中的关键参与者。在多个组学水平上了解该通路对COAD的影响对于推进癌症免疫治疗和精准医学至关重要。本研究旨在调查cGAS-STING相关基因与COAD之间的关系，分析基因突变、拷贝数变异、DNA甲基化和基因表达，以揭示该通路对COAD预后的影响。利用来自TCGA和GEO数据库的多组学测序数据，确定了cGAS-STING通路中的关键核心基因，并通过PCR和蛋白质免疫印迹分析进一步验证。评估了CASP8和RIPK1基因的突变和拷贝数变异、DNA甲基化差异模式以及特定基因的mRNA表达水平，以确定它们对COAD预后的影响。通过组织样本进行的验证突出了NLRC3、CASP1、AIM2和CXCL10作为cGAS-STING通路中的核心基因。我们的研究结果表明，CASP8和RIPK1的突变和拷贝数变异、DNA甲基化差异模式以及基因表达水平的改变显著影响COAD的预后。cGAS-STING通路中核心基因的鉴定，特别是NLRC3、CASP1、AIM2和CXCL10，已促成了一种通过免疫细胞浸润预测不良肿瘤结局的预后模型的开发。本研究为cGAS-STING通路在COAD中的作用机制提供了有价值的见解，并为癌症免疫治疗和精准医学的未来研究提供了潜在方向。
