赣南医学院学报2024，Vol.44Issue(1) ：27-34.DOI:10.3969/j.issn.1001-5779.2024.01.005

肝细胞癌双硫死亡相关LncRNA预后模型的构建和验证

Construction and validation of a prognostic model for disulfidptosis-associated LncRNA in hepatocellular carcinoma

方霞 孙江云 袁丰华
赣南医学院学报2024，Vol.44Issue(1) ：27-34.DOI:10.3969/j.issn.1001-5779.2024.01.005
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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据

肝细胞癌双硫死亡相关LncRNA预后模型的构建和验证

Construction and validation of a prognostic model for disulfidptosis-associated LncRNA in hepatocellular carcinoma

方霞 1孙江云 2袁丰华1
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作者信息

  • 1. 赣南医科大学基础医学院
  • 2. 赣南医科大学第一临床医学院,江西 赣州 341000
  • 折叠

摘要

目的:评估双硫死亡相关LncRNA在肝细胞癌(Hepatocellular carcinoma,HCC)患者中作为预后指标的潜在价值.方法:从TCGA数据库中获取HCC的RNA-Seq和临床信息数据,从相关文献中获得10个双硫死亡相关基因,通过共表达分析获得双硫死亡相关LncRNA.然后利用单因素Cox回归、Lasso风险回归分析和多因素Cox回归构建基于双硫死亡相关LncRNA的预后模型,根据训练集的风险评分中位值将HCC样本划分高、低风险组,通过K-M生存曲线、ROC曲线、主成分分析(PCA)以及C-指数评估模型效果.此外,对高、低风险组差异基因进行GSEA富集分析,并对高、低风险组进行免疫功能差异分析和免疫治疗效果分析.结果:从TCGA-LIHC数据库筛选得到320个双硫死亡相关LncRNA,单因素Cox回归分析得到40个与患者预后相关的LncRNA(P＜0.05),LASSO风险回归和多因素Cox回归分析构建了6个双硫死亡相关LncRNA的预后模型(ELFN1-AS1、AL049840.2、MKLN1-AS、CYTOR、AL161645.1和AC069307.1),且K-M生存曲线、ROC曲线、主成分分析(PCA)以及C-指数验证了该模型具有良好的预测能力.对高、低风险组差异基因进行GO和KEGG富集分析,GO富集分析显示,生物学过程主要富集在外部封装结构组织,细胞组分主要富集在含胶原的细胞外基质,分子功能主要富集在细胞外基质成分.KEGG主要富集在PI3K/AKT信号通路.此外,对高低风险组差异表达基因进行功能富集分析,发现高风险组主要富集在细胞外基质受体途径,而低风险组主要富集在药物代谢细胞色素p450途径.采用GSEABase包分析高、低风险组免疫功能之间的差异,结果显示高风险组抗原呈递细胞共刺激(APC_CO_stimulation)、趋化因子受体(CCR)、主要组织相容性复合体Ⅰ类呈递(MHC_class_Ⅰ)、副炎症和辅助性T细胞2(Th2)的表达高于低风险组,高风险组的TIDE评分高于低风险组.结论:基于TCGA数据库构建了具有良好预测性能的HCC预后模型,为进一步研究双硫死亡相关LncRNA在肝细胞癌中的作用提供了新思路.

Abstract

Objective:To evaluate the potential value of disulfide death-related LncRNA as prognostic indicators in patients with hepatocellular carcinoma(HCC).Methods:RNA-Seq and clinical information data of HCC were obtained from the TCGA database,and 10 bisulfide death-associated genes were obtained from related literature,and bisulfide death-associated LncRNA were obtained by co-expression analysis.Then,a prognostic model based on bisulfite death-associated LncRNA was constructed by using one-factor Cox regression,Lasso risk regression analysis,and multifactor Cox regression.The HCC samples were divided into high-risk and low-risk groups based on the median risk score values of the training set,and the model effects were assessed by K-M survival and ROC curves,principal component analysis(PCA),and C-index.In addition,GSEA enrichment analysis of differential genes between the two groups was performed,and differential analysis of immune function and immunotherapy effect were also analyzed.Results:Altogether 320 bisulfide death-associated LncRNA were screened from the TCGA-LIHC database,40 LncRNA associated with patients'prognosis were obtained by univariate Cox analysis(P＜0.05),and 6 prognostic models of bisulfide death-associated LncRNA were constructed by Lasso risk regression and multivariate Cox regression(ELFN1-AS1,AL049840.2,MKLN1-AS,CYTOR,AL161645.1,and AC069307.1),and the K-M survival and ROC curves,principal component analysis(PCA),and the C-index verified the good predictive ability of the models.GO and KEGG enrichment analyses were performed on the differential genes of the high-risk and low-risk groups.GO enrichment analysis showed that biological processes were mainly enriched in external encapsulating structure organisation,cellular components were mainly enriched in collagen-containing extracellular matrix,molecular functions are mainly enriched in extracellular matrix structural constituents.KEGG was mainly enriched in the PI3K/AKT signaling pathway.In addition,functional enrichment analysis of differentially expressed genes in the high-and low-risk groups revealed that the high-risk group was mainly enriched in the extracellular matrix receptor pathway,while the low-risk group was mainly enriched in the drug metabolism cytochrome p450 pathway.The GSEABase package was used to analyze the differences between the immune functions of the high-risk and low-risk groups and the results showed that the high-risk group had a higher prevalence of antigen-presenting cell co-stimulation(APC_CO_stimulation),chemokine receptor(CCR),major histocompatibility complex class Ⅰ presentation(MHC_class_Ⅰ),parainflammation and helper T-cell 2(Th2)expression were higher than those in the low-risk group,and the TIDE score was higher in the high-risk group than that in the low-risk group.Conclusion:A prognostic model of HCC with good predictive performance was constructed based on the TCGA database,which provides a new idea for further research on the role of disulfide death-associated LncRNA in hepatocellular carcinoma.

关键词

肝细胞癌/癌症基因组图谱/双硫死亡/长非编码RNA/预后模型

Key words

Hepatocellular carcinoma/The cancer genome atlas/Disulfide death/Long non-coding RNA/Prognostic model

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出版年

2024
赣南医学院学报
赣南医学院

赣南医学院学报

影响因子：0.622
ISSN：1001-5779
参考文献量30
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