利用GEO数据库分析糖尿病患者冠心病易感相关基因表达差异的生物信息学分析

Bioinformatics analysis of gene expression differences in susceptibility to coronary heart disease in diabetic patients using GEO database

目的 应用GEO数据库分析单纯糖尿病患者与合并冠状动脉粥样硬化性心脏病(CAD)的糖尿病(DM)患者相关基因的表达差异。方法 检索基因表达数据库(GEO)并筛选DM患者合并CAD的DM患者相关基因表达谱数据。时间截点选择2021年5月,筛选条件选择“Diabetes”及“Coronary Heart Disease”,物种类型选择“human”。使用GEO2R分析DM患者合并CAD的差异表达基因,并对单纯DM患者与合并CAD的DM患者间的通路富集情况做KEGG分析,而后使用PPI分析找出关键基因及其蛋白靶标;并以同期健康体检人群及单纯CAD患者作为参照组,对单纯DM、单纯CAD及合并CAD的DM患者差异基因表达情况进行比较。结果 从选定数据集共筛选出差异基因32 322个,设置筛选条件为组间表达量的比值Log2FC>2且P<0.05,共筛选出差异基因76个,其中上调基因23个,下调基因53个。DM与合并CAD的DM有10条显著差异性富集信号通路(P<0.05)。GO功能分析得到显著富集条目30个,其中10个(33.3%)与生物过程(BP)相关,10个(33.3%)与细胞组分(CC)相关,10个(33.3%)与分子功能(MF)相关。PTC与对照组显著差异基因共计42个,其中排名前10的分别是MYC、C3、AGTR1、PPARG、ADRB3、ACE、NOS3、MTHFR、UTS2、PON2;合并CAD组患者的MYC、C3、AGTR1、PPARG、ADRB3、ACE及UTS2基因表达水平明显高于单纯DM组,而NOS3、MTHFR及PON2基因表达水平明显低于单纯DM组(均P<0.05);单纯DM组与单纯CAD组间MYC、C3、AGTR1、PPARG、ADRB3、ACE、NOS3及MTHFR基因表达水平差异无统计学意义,而单纯CAD组的UTS2明显低于单纯DM组,PON2明显高于单纯DM组(均P<0.01)。结论 DM合并CAD发生的关键影响基因主要包括MYC、C3、AGTR1、PPARG、ADRB3、ACE、NOS3、MTHFR、UTS2、PON2,可能通过磷脂酰肌醇3-激酶/蛋白激酶B信号通路(PI3K/AKT signaling pathway)、病毒致癌作用(Viral carcinogenesis)、黏着斑(Focal adhesion)、Wnt信号通路(Wnt signaling pathway)等对DM发生合并CAD的影响。

Objective The GEO database was used to analyze the differences in the expression of related genes between patients with simple diabetes and diabetes(DM) patients with coronary heart disease(CAD).Methods The Gene Expression Omnibus(GEO) was searched and the DM patients-related gene expression profile data of DM patients with CAD were screened.The time cutoff is May 2021,the screening criteria are "Diabetes" and "Coronary Heart Disease",and the species type is "human".GEO2R was used to analyze the differentially expressed genes of DM patients with CAD,and KEGG analysis was performed on the pathway enrichment between DM patients with simple DM and DM patients with CAD,and then PPI analysis was used to identify key genes and their protein targets;The physical examination population and patients with pure CAD were used as the reference group to compare the differential gene expression of pure DM,pure CAD and DM patients with CAD.Results A total of 32,322 differential genes were screened from the selected data set.The screening conditions were set as the ratio of expression between groups Log2FC>2 and P<0.05.A total of 76 differential genes were screened,including 23 up-regulated genes and 53 down-regulated genes.DM and DM with CAD had 10 significantly different enriched signaling pathways(P<0.05).GO functional analysis yielded 30 significantly enriched entries,of which 10(33.3%) were related to biological processes(BP),10(33.3%) were related to cellular components(CC),and 10(33.3%) were related to molecular functions(MF)related.A total of 42 genes were significantly different between PTC and the control group,of which the top 10 were MYC,C3,AGTR1,PPARG,ADRB3,ACE,NOS3,MTHFR,UTS2,PON2;MYC,C3,AGTR1,PPARG in the combined CAD group,ADRB3,ACE and UTS2 gene expression levels were significantly higher than those in the simple DM group,while NOS3,MTHFR and PON2 gene expression levels were significantly lower than those in the simple DM group (all P<0.05).There was no significant difference in the gene expression levels of AGTR1,PPARG,ADRB3,ACE,NOS3 and MTHFR,while UTS2 in the simple CAD group was significantly lower than that in the simple DM group,and PON2 was significantly higher than that in the simple DM group (all P<0.01).Conclusion The key genes affecting the occurrence of DM combined with CAD mainly include MYC,C3,AGTR1,PPARG,ADRB3,ACE,NOS3,MTHFR,UTS2,PON2,which may be through the phosphatidylinositol 3-kinase/protein kinase B signaling pathway(PI3K/AKT signaling pathway).signaling pathway,viral carcinogenesis,focal adhesion,Wnt signaling pathway and other effects on DM combined with CAD.