A Prognostic Model Using Immune-Related Genes for Colorectal Cancer.

A Prognostic Model Using Immune-Related Genes for Colorectal Cancer.
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使用免疫相关基因治疗结直肠癌的预后模型

DOI:
10.3389/fcell.2022.813043
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发表时间:
2022
影响因子:
5.5
通讯作者:
Song W
Song W
中科院分区:
生物学2区
文献类型:
--
作者:
Feng W;Zhang Y;Liu W;Wang X;Lei T;Yuan Y;Chen Z;Song W

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有证据表明,免疫基因在结直肠癌(CRC)的发生和发展中起着关键作用。将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随机分为训练集、测试集和外部验证集。差异表达基因(DEG)分析,单变量考克斯回归,和最小绝对收缩和选择算子(LASSO)被用来确定生存相关的免疫基因,并开发一个预后模型。采用受试者工作特征(ROC)分析和主成分分析(PCA)评价风险模型的区分度。使用人类蛋白质图谱(HPA)数据库、结直肠细胞系和新鲜CRC和邻近组织验证预测的模型基因。为了了解IRGs与免疫侵袭和TME之间的关系,我们分析了免疫细胞的含量,并使用CIBERSORT和ESTIMATE算法对TME进行评分。最后,利用肿瘤药物敏感基因组学(GDSC)预测不同危险评分组的潜在敏感化疗药物。共筛选了491个IRG,其中14个IRG被鉴定为与总生存期(OS)显著相关,并用于构建CRC患者的免疫相关基因(IRG)预后标记(IRGSig)。校正图显示列线图具有较强的预测能力。PCA和ROC分析进一步验证了该14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,在肿瘤发生发展过程中,从早期到中期到晚期,肿瘤微环境发生了显著变化,这可能是肿瘤恶化的重要因素。最后,我们选择了六种常用的化疗药物,这些药物有可能用于治疗CRC。总之,免疫基因被用于构建结直肠癌患者的预后模型,并使用多种方法来测试该模型的准确性。此外,我们还从免疫细胞浸润和TME两个方面探讨了结直肠癌的免疫机制。此外,我们还评估了许多常用化疗药物在具有不同风险因素的个体中的治疗敏感性。最后,本文对CRC免疫风险模型和免疫机制进行了深入的研究。
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.
DOI: 10.1158/1078-0432.ccr-16-3133
发表时间: 2017-08-01
期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子: --
作者:
Kato S;Goodman A;Walavalkar V;Barkauskas DA;Sharabi A;Kurzrock R
通讯作者: Kurzrock R
DOI: 10.1016/j.tranon.2019.10.018
发表时间: 2020-02-01
影响因子: 5
作者:
Dobosz, Paula;Stempor, Przemyslaw A.;Leibowitz-Amit, Raya
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DOI: 10.3389/fgene.2021.669694
发表时间: 2021
影响因子: 3.7
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DOI: 10.1002/ijc.32993
发表时间: 2020-05-22
影响因子: 6.4
作者:
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通讯作者: Feugeas, Jean P.