Development and validation of an immune-related gene signature for prognosis in Lung adenocarcinoma

IF 1.9 4区 生物学 Q4 CELL BIOLOGY
Zehuai Guo, Xiangjun Qi, Zeyun Li, Jianying Yang, Zhe Sun, Peiqin Li, Ming Chen, Yang Cao
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引用次数: 0

Abstract

The most common type of lung cancer tissue is lung adenocarcinoma. The TCGA-LUAD cohort retrieved from the TCGA dataset was considered the internal training cohort, while GSE68465 and GSE13213 datasets from the GEO database were used as the external test cohort. The TCGA-LUAD cohort was classified into two immune subtypes using single-sample gene set enrichment analysis of the immune gene set and unsupervised clustering analysis. The ESTIMATE algorithm, the CIBERSORT algorithm, and HLA family expression levels again validated the reliability of this typing. We performed Venn analysis using immune-related genes from the immport dataset and differentially expressed genes from the subtypes to retrieve differentially expressed immune genes (DEIGs). In addition, DEIGs were used to construct a prognostic model with the least absolute shrinkage and selection operator regression analysis. A reliable risk model consisting of 11 DEIGs, including S100P, INHA, SEMA7A, INSL4, CD40LG, AGER, SERPIND1, CD1D, CX3CR1, SFTPD, and CD79A, was then built, and its reliability was further confirmed by ROC curve and calibration plot analysis. The high-risk score subgroup had a poor prognosis and a lower tumour immune dysfunction and exclusion score, indicating a greater likelihood of anti-PD-1/cytotoxic T lymphocyte antigen 4 benefit.

Abstract Image

肺腺癌预后免疫相关基因标记的开发和验证
最常见的肺癌组织类型是肺腺癌。从TCGA数据集中检索的TCGA- luad队列作为内部训练队列,而从GEO数据库中检索的GSE68465和GSE13213数据集作为外部测试队列。利用免疫基因集的单样本基因集富集分析和无监督聚类分析将TCGA-LUAD队列划分为两个免疫亚型。估计算法、CIBERSORT算法和HLA家族表达水平再次验证了该分型的可靠性。我们使用输入数据集中的免疫相关基因和来自亚型的差异表达基因进行了Venn分析,以检索差异表达免疫基因(DEIGs)。此外,采用DEIGs构建了绝对收缩最小的预后模型,并进行了选择算子回归分析。建立由S100P、INHA、SEMA7A、INSL4、CD40LG、AGER、SERPIND1、CD1D、CX3CR1、SFTPD、CD79A等11个设计因子组成的可靠风险模型,并通过ROC曲线和标定图分析进一步验证其可靠性。高危评分亚组预后较差,肿瘤免疫功能障碍和排斥评分较低,提示抗pd -1/细胞毒性T淋巴细胞抗原4获益的可能性较大。
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来源期刊
IET Systems Biology
IET Systems Biology 生物-数学与计算生物学
CiteScore
4.20
自引率
4.30%
发文量
17
审稿时长
>12 weeks
期刊介绍: IET Systems Biology covers intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. Papers that analyse genomic data in order to identify variables and basic relationships between them are considered if the results provide a basis for mathematical modelling and simulation of cellular dynamics. Manuscripts on molecular and cell biological studies are encouraged if the aim is a systems approach to dynamic interactions within and between cells. The scope includes the following topics: Genomics, transcriptomics, proteomics, metabolomics, cells, tissue and the physiome; molecular and cellular interaction, gene, cell and protein function; networks and pathways; metabolism and cell signalling; dynamics, regulation and control; systems, signals, and information; experimental data analysis; mathematical modelling, simulation and theoretical analysis; biological modelling, simulation, prediction and control; methodologies, databases, tools and algorithms for modelling and simulation; modelling, analysis and control of biological networks; synthetic biology and bioengineering based on systems biology.
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