现代检验医学杂志2024,Vol.39Issue(2) :86-90.DOI:10.3969/j.issn.1671-7414.2024.02.016

基于TCGA数据库构建肝细胞癌双硫死亡相关基因(DRGs)预后风险模型及评价

Construction and Evaluation of the Disulfidptosis-Related Genes(DRGs)Prognostic Risk Model for Hepatocellular Carcinoma Based on TCGA Database

王结珍 梁培松
现代检验医学杂志2024,Vol.39Issue(2) :86-90.DOI:10.3969/j.issn.1671-7414.2024.02.016

基于TCGA数据库构建肝细胞癌双硫死亡相关基因(DRGs)预后风险模型及评价

Construction and Evaluation of the Disulfidptosis-Related Genes(DRGs)Prognostic Risk Model for Hepatocellular Carcinoma Based on TCGA Database

王结珍 1梁培松1
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作者信息

  • 1. 中山市人民医院检验医学中心,广东中山 528403
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摘要

目的 基于癌症基因组图谱(the cancer genome atlas,TCGA)数据库构建肝细胞癌(hepatocellular carcinoma,HCC)双硫死亡相关基因(disulfidptosis-related genes,DRGs)预后风险模型及评价.方法 通过生物信息学方法分析TCGA数据库中 371 例HCC样本及 50 例癌旁样本中 15 个DRGs的表达情况,并进行基因本体(gene ontology,GO)功能注释和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析、Kaplan-Meier(KM)生存分析;通过单因素COX回归分析筛选出有统计学意义的DRGs,通过LASSO回归分析及多因素COX回归分析筛选出关键DRGs构建预后风险模型,并根据风险评分将HCC患者分为高风险组和低风险组,制作KM生存曲线和时间依赖的受试者工作特征(receiver operator characteristic,ROC)曲线进行验证评价.结果 与癌旁样本相比,HCC样本 15 个DRGs中FLNA,MYH9,TLN1,ACTB,MYL6,CAPZB,DSTN,ACTN4,SLC7A11,INF2,CD2AP,PDLIM1 和FLNB均表达上调,且差异具有统计学意义(t=1 793~6 310,均P<0.001);经GO功能注释和KEGG富集分析显示,DRGs主要与肌动蛋白细胞骨架和细胞黏附相关的生物过程或途径密切相关.经KM生存分析结果显示,SLC7A11,INF2,CD2AP,MYL6,ACTB高表达组生存率低于低表达组[HR=1.46(1.03~2.07)~1.93(1.36~2.75),均P<0.05].通过单因素COX回归分析、LASSO分析及多因素COX回归分析构建预后风险模型riskscore=(0.247×SLC7A11)+(0.289×INF2)+(0.076×CD2AP)+(0.06×MYL6);计算样本的风险评分,风险评分越高,预后不良的HCC患者人数越多;KM生存分析显示高风险组的总生存率比低风险组低;1,3,5 年的AUC值分别为 0.709,0.661 和 0.648;通过多因素COX回归分析表明SLC7A11[HR=1.832(1.274~2.636),P=0.001]是独立的预后危险因素.结论 四个DRGs构建的预后风险模型在预测HCC患者预后情况有一定的作用.

Abstract

Objective To construct and evaluate a disulfidptosis-related genes(DRGs)prognostic risk model for hepatocellular carcinoma(HCC)based on the cancer genome atlas(TCGA)database.Methods The expression of 15 DRGs in 371 HCC samples and 50 adjacent cancer samples in the TCGA database was analyzed using bioinformatics methods,and then gene ontology(GO)functional annotation,Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis and Kaplan-Meier(KM)survival analysis were performed.Statistical significant DRGs were screened through univariate COX regression analysis,and key DRGs were selected through LASSO regression analysis and multivariate COX regression analysis to construct a prognostic risk model.HCC patients were divided into high-risk and low-risk groups based on risk scores,and the KM survival curves and time-dependent receiver operator characteristic(ROC)curves were created to validate and evaluate prognostic risk models.Results Compared with the adjacent cancer samples,FLNA,MYH9,TLN1,ACTB,MYL6,CAPZB,DSTN,ACTN4,SLC7A11,INF2,CD2AP,PDLIM1,and FLNB were all upregulated in the 15 DRGs of HCC samples,and the differences were significant(t=1 793~6 310,all P<0.001).According to GO functional annotation and KEGG enrichment analysis,DRGs were closely related to biological processes or pathways related to actin cytoskeleton and cell adhesion.The results of KM survival analysis showed that the survival rate of the high expression group of SLC7A11,INF2,CD2AP,MYL6,and ACTB were lower than that of the low expression group[HR=1.46(1.03~2.07)~1.93(1.36~2.75),all P<0.05].Univariate COX regression analysis,LASSO analysis,and multivariate COX regression analysis were used to construct a prognostic risk model,with risk score=(0.247×SLC7A11)+(0.289×INF2)+(0.076×CD2AP)+(0.06×MYL6).The risk score of the sample in this model was calculated,and the higher the risk score,the more HCC patients with poor prognosis.KM survival analysis showed that the overall survival rate of the high-risk group was lower than that of the low-risk group.The AUC values for 1,3,and 5 years were 0.709,0.661,and 0.648,respectively.Multivariate COX regression analysis showed that SLC7A11[HR=1.832(1.274~2.636),P=0.001]was an independent prognostic risk factor.Conclusion The prognostic risk model was constructed by four DRGs,which has a certain role in predicting the prognosis of HCC patients.

关键词

肝细胞癌/癌症基因组图谱/双硫死亡相关基因/预后风险模型

Key words

hepatocellular carcinoma/the cancer genome atlas/disulfidptosis-related genes/prognostic risk model

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出版年

2024
现代检验医学杂志
陕西省临床检验中心,陕西省人民医院

现代检验医学杂志

CSTPCD
影响因子:0.713
ISSN:1671-7414
参考文献量15
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