基于双硫死亡的心肌缺血再灌注损伤相关风险基因筛选及分析

Analysis of risk genes associated with disulfidptosis-related myocardial ischemia-reperfusion injury

摘要

目的 筛选基于双硫死亡的心肌缺血再灌注损伤（myocardial ischemia reperfusion injury，MIRI）相关风险基因及探索其可能的作用途径。 方法 用R语言limma分析并筛选MIRI相关风险基因24 h组与Control组之间的差异表达基因。基于GO和KEGG数据库利用 R语言cluterProfiler包对其进行功能富集分析。根据双硫死亡基因集以及GSE160516的表达数据，利用R语言GSVA包中的ssgsea法对其进行富集分析，并利用Venn图获得心肌缺血再灌注中双硫死亡相关基因的表达。用R语言psych包中的corr.test计算双硫死亡相关基因与凋亡因子、线粒体、铁死亡及炎症等相关基因的相关性，并绘制热图。利用R语言Mfuzz包来进行不同时间点心肌缺血再灌注转录组数据的表达模式聚类分析并利用Venn图获取时序性差异表达的双硫死亡基因。 结果 本研究共筛选出17个差异表达双硫死亡相关基因，经过双硫死亡相关基因与炎症、凋亡、铁死亡、线粒体基因相关性分析，以及双硫死亡相关基因与心肌缺血再灌注时序性分析的差异表达基因筛选，最终得到双硫死亡相关基因Flna、Myl6、Tln1在MIRI不同时间的特异性表达。 结论 Flna、Myl6、Tln1在MIRI中可能起着关键作用，其基于双硫死亡同时与线粒体相关基因密切相关，可作为MIRI患者风险因素的筛选指标。

Abstract

Objective To select genes associated with disulfidptosis-related myocardial ischemia-reperfusion injury（MIRI），and to explore their possible pathways of action. Methods We selected differentially expressed genes associated with MIRI between the 24 h group and the control group with the use of the limma R package； performed functional enrichment analysis on the genes through the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases with the use of the clusterProfiler R package；conducted enrichment analysis based on disulfidptosis-related gene set and GSE160516 expression data using the ssgsea method of the GSVA R package，and identified the expression of disulfidptosis-related genes in myocardial ischemia-reperfusion using a Venn diagram；calculated the correlations between disulfidptosis-related genes and genes associated with apoptosis factors，mitochondria，ferroptosis，and inflammation using the corr. test of the psych R package，and generated a heatmap； and clustered the expression patterns of MIRI transcriptome data at different time points using the Mfuzz R package，and identified time series-related differentially expressed disulfidptosis-related genes using a Venn diagram. Results A total of 17 differentially expressed disulfidptosis-related genes were determined in this study. Through correlation analysis of disulfidptosis-related genes and genes associated with inflammation，apoptosis，ferroptosis，and mitochondria as well as analysis of time series-related differentially expressed genes associated with disulfidptosis during myocardial ischemia-reperfusion，we finally identified the specific expression of disulfidptosis-related Flna，Myl6，and Tln1 genes at different time points pf MIRI. Conclusion The Flna，Myl6，and Tln1 gens may play crucial roles in MIRI，and these disulfidptosis-related genes are closely associated with mitochondria-related genes，which can be screening indicators for risk factors in patients with MIRI.

关键词

心肌缺血再灌注 / 双硫死亡 / 生信分析 / 风险因素筛选指标

Key words

myocardial ischemia-reperfusion / disulfidptosis / bioinformatics analysis / risk factor screening indicator

基金资助

国家自然科学基金资助项目(82060340)

贵州省科技计划资助项目(黔科合基础-ZK（2023）一般330)

贵州省普通高等学校青年科技人才成长资助项目(黔教合KY字〔2021〕157)

山东省证据鉴识重点实验室开放课题资助项目(2018KFKT6)

国家级大学生创新创业训练资助项目(202210660025;202110660004)