Feng Wei, Zhang Yongxin, Liu Wenwei, Wang Xiaofeng, Lei Tianxiang, Yuan Yujie, Chen Zehong, Song Wu
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2022 Feb 15;10:813043. doi: 10.3389/fcell.2022.813043. eCollection 2022.
There is evidence suggesting that immune genes play pivotal roles in the development and progression of colorectal cancer (CRC). Colorectal carcinoma patient data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were randomly classified into a training set, a test set, and an external validation set. Differentially expressed gene (DEG) analyses, univariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) were used to identify survival-associated immune genes and develop a prognosis model. Receiver operating characteristic (ROC) analysis and principal component analysis (PCA) were used to evaluate the discrimination of the risk models. The model genes predicted were verified using the Human Protein Atlas (HPA) databases, colorectal cell lines, and fresh CRC and adjacent tissues. To understand the relationship between IRGs and immune invasion and the TME, we analyzed the content of immune cells and scored the TME using CIBERSORT and ESTIMATE algorithms. Finally, we predicted the potential sensitive chemotherapeutic drugs in different risk score groups by the Genomics of Drug Sensitivity in Cancer (GDSC). A total of 491 IRGs were screened, and 14 IRGs were identified to be significantly related to overall survival (OS) and applied to construct an immune-related gene (IRG) prognostic signature (IRGSig) for CRC patients. Calibration plots showed that nomograms have powerful predictive ability. PCA and ROC analysis further verified the predictive value of this fourteen-gene prognostic model in three independent databases. Furthermore, we discovered that the tumor microenvironment changed significantly during the tumor development process, from early to middle to late stage, which may be an essential factor for tumor deterioration. Finally, we selected six commonly used chemotherapeutic drugs that have the potential to be useful in the treatment of CRC. Altogether, immune genes were used to construct a prognosis model for CRC patients, and a variety of methods were used to test the accuracy of this model. In addition, we explored the immune mechanisms of CRC through immune cell infiltration and TME in CRC. Furthermore, we assessed the therapeutic sensitivity of many commonly used chemotherapeutic medicines in individuals with varying risk factors. Finally, the immune risk model and immune mechanism of CRC were thoroughly investigated in this paper.
有证据表明免疫基因在结直肠癌(CRC)的发生和发展中起关键作用。来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的结直肠癌患者数据被随机分为训练集、测试集和外部验证集。采用差异表达基因(DEG)分析、单变量Cox回归和最小绝对收缩和选择算子(LASSO)来识别与生存相关的免疫基因并建立预后模型。采用受试者工作特征(ROC)分析和主成分分析(PCA)来评估风险模型的判别能力。使用人类蛋白质图谱(HPA)数据库、结直肠癌细胞系以及新鲜的CRC组织和癌旁组织对预测的模型基因进行验证。为了了解免疫相关基因(IRGs)与免疫浸润和肿瘤微环境(TME)之间的关系,我们使用CIBERSORT和ESTIMATE算法分析了免疫细胞的含量并对TME进行评分。最后,我们通过癌症药物敏感性基因组学(GDSC)预测了不同风险评分组中潜在的敏感化疗药物。共筛选出491个IRGs,确定其中14个IRGs与总生存期(OS)显著相关,并将其应用于构建CRC患者的免疫相关基因(IRG)预后特征(IRGSig)。校准图显示列线图具有强大的预测能力。PCA和ROC分析进一步验证了这个十四基因预后模型在三个独立数据库中的预测价值。此外,我们发现肿瘤微环境在肿瘤发展过程中从早期到中期再到晚期发生了显著变化,这可能是肿瘤恶化的一个重要因素。最后,我们选择了六种常用的可能对CRC治疗有用的化疗药物。总之,利用免疫基因构建了CRC患者的预后模型,并使用多种方法测试了该模型的准确性。此外,我们通过CRC中的免疫细胞浸润和TME探索了CRC的免疫机制。此外,我们评估了许多常用化疗药物对不同风险因素个体的治疗敏感性。最后,本文对CRC的免疫风险模型和免疫机制进行了深入研究。