中国动脉硬化杂志2023，Vol.31Issue(11)：938-944,7.DOI:10.20039/j.cnki.1007-3949.2023.11.003
基于生物信息学探讨与铜死亡相关的早、晚期动脉粥样硬化的差异基因及潜在标志物
Study on differential genes and potential biomarkers of early and advanced athero-sclerosis related to cuproptosis based on bioinformatics
摘要
Abstract
Aim To screen the early and advanced atherosclerosis differential genes associated with cuproptosis by bioinformatic methods,and analyze their mechanisms of action,and predict potential biomarkers.Methods The information related to early and advanced atherosclerosis(GSE28829 and GSE43292 data sets)was downloaded from GEO database and standardized.19 cuproptosis genes were obtained from the literature.Difference analysis,enrichment a-nalysis,consensus clustering algorithm,principal component analysis,immune cell infiltration and screening core genes were used to find their action mechanisms and potential biomarkers.Results Finally,10 differential genes related to cuproptosis were screened.The correlation analysis of differential genes related to cuproptosis showed a strong positive correlation between GLS and DBT(r=0.78,P＜0.001),while NLRP3 showed a strong negative correlation with DBT and GLS(r=-0.62,P＜0.001).GO enrichment analysis of differential genes related to cuproptosis was mainly related to copper ion transport and copper homeostasis,and KEGG analysis showed that it was mainly enriched in platinum resist-ance,mineral absorption and central carbon metabolic pathway in cancer.The PPI network analysis and MCODE were used to screen core genes.The results of immune cell infiltration showed that M2 macrophages,M0 macrophages,resting CD4 memory T cells,and CD8+T cells were dominant(P＜0.05).The correlation analysis of differential genes related to immune cells and cuproptosis showed that in the early stage of atherosclerosis,GLS was strongly positively correlated with activated NK cells(r=0.52,P＜0.001),FDX1 and SLC31A1 was strongestly negatively correlated with CD8+T cells(r=-0.51,P＜0.001);in the advanced stage of atherosclerosis,FDX1 was strongestly positively correlated with M0 macro-phages(r=0.58,P＜0.001)and FDX1 was strongestly negatively correlated with CD8+T cells(r=-0.55,P＜0.001).Principal component analysis showed that two subtypes Cl and C2 could be clearly distinguished according to the expression of cuproptosis-related differential genes.Conclusion The immune-related changes between cuproptosis and the devel-opment of atherosclerosis may be the key to the diagnosis and treatment of early and advanced atherosclerosis,and the core genes SLC31A1,MTF1,ATP7B and ATP7A may be potential markers and therapeutic targets for the development of ather-osclerosis.关键词
动脉粥样硬化/铜死亡/差异分析/免疫细胞浸润/生物信息学Key words
atherosclerosis/cuproptosis/difference analysis/immune cell infiltration/bioinformatics分类
临床医学引用本文复制引用
房慧琴,马晓维,陈秋,崔淑菲,赵军绩,赵宗芹,臧运华..基于生物信息学探讨与铜死亡相关的早、晚期动脉粥样硬化的差异基因及潜在标志物[J].中国动脉硬化杂志,2023,31(11):938-944,7.基金项目
山东省中医药科技发展计划项目(2019-0605) （2019-0605）
2018-2019年度青岛市中医药科研计划项目(2019-zyy015) （2019-zyy015）
青岛市2020年度医药科研指导计划项目(2020-WJZD226) （2020-WJZD226）
2022年度医药卫生科研指导项目(2022-WJZD041) （2022-WJZD041）
