首页|基于细胞焦亡与免疫相关基因构建及验证肝细胞癌预后风险模型

基于细胞焦亡与免疫相关基因构建及验证肝细胞癌预后风险模型

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目的:利用生物信息学方法构建并验证细胞焦亡与免疫相关基因的肝细胞癌预后风险模型,根据其风险评分探索免疫相关性特征,以指导个性化免疫治疗.方法:从TCGA、GEO官网分别下载TCGA-LIHC和GSE14520基因表达谱,从INNATEDB和IMMPORT官网下载免疫相关基因.以TCGA为训练组,GEO为测试组,对训练组细胞焦亡基因表达谱采用Cox回归分析,筛选预后相关基因进行共识聚类分组,提取分组间差异基因与免疫相关基因的交集基因,对交集基因应用单因素Cox和Lasso回归分析,得到预后相关风险评分模型.根据训练组风险中位值划分高低风险组,利用测试组验证模型可行性,最后探索训练组富集分析(GO、KEGG、GSEA)、免疫相关性分析及模型基因蛋白表达情况.结果:共筛选出9个可靠的风险模型基因(ICAM1、S100P、FABP3、CCL20、HRG、IGHM、SPP1、C4BPA、C6).GO富集分析显示风险差异基因主要参与各种代谢过程.KEGG富集分析显示风险差异基因主要参与补体和凝血级联信号通路.GSEA富集分析显示高风险组与致癌途径的激活密切相关.在免疫浸润、免疫相关通路及免疫检查点中发现高低风险组具有显著差异.HPA数据库证明ICAM1、S100P、SPP1模型基因免疫组化表达存在明显差异.结论:9个基因组成的风险模型可能成为肝细胞癌发生、发展及预后相关的潜在生物标志物,并为优化肝细胞癌的诊治提供新线索.
Prognostic risk model of hepatocellular carcinoma developed and validated based on pyroptosis and immune-related genes
Objective:Bioinformatics methods was used to develop and validate a prognostic risk model of pyroptosis and immune-related genes in hepatocellular carcinoma,and to explore immune correlated features based on the risk scores to guide person-alised immunotherapy.Methods:TCGA-LIHC and GSE14520 gene expression profiles were downloaded from TCGA and GEO official websites respectively,and immune-related genes were downloaded from INNATEDB and IMMPORT websites.TCGA as the training group and GEO as the test group,Cox regression analysis was performed on expression profile of pyroptosis gene in training group.Selected prognostic related genes for consensus clustering,and extracted the intersection genes between difference genes and immune-related genes.Univariate Cox and Lasso regression analysis were applied to the intersection genes to obtain the prognosis related risk model.High-and low-risk groups were divided according to the median risk of training group,and the feasibility of model was verified by the test group.Finally,the enrichment analysis(GO,KEGG,GSEA),immune correlation analysis and model gene,protein ex-pression of training group were discussed.Results:Nine reliable risk model genes were screened(ICAM1,S100P,FABP3,CCL20,HRG,IGHM,SPP1,C4BPA,C6).GO enrichment analysis showed that risk differential genes mainly existed in various metabolic processes.KEGG enrichment analysis showed that risk differential genes were mainly involved in complement and coagulation cascade signal pathways.CSEA showed that high-risk group was closely related to the activation of carcinogenic pathway.High-and low-risk groups have significant differences in immune infiltration,immune related pathways and immune checkpoints.HPA database showed that there were significant differences in immunohistochemical expression of ICAM1,S100P and SPP1 model genes.Conclusion:The risk model composed of 9 genes may become a potential biomarker related to the occurrence,development and prognosis of hepatocel-lular carcinoma,and provide new clues for optimizing the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinomaPyroptosisImmune-related genesPrognosisImmune infiltration

谢彬、任婷婷

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贵州医科大学医学检验学院临床生化教研室,贵阳 550004

肝细胞癌 细胞焦亡 免疫相关基因 预后 免疫浸润

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(5)
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