Li Chan, Liu Zhaoya
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Department of Geriatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Int J Gen Med. 2021 Aug 10;14:4337-4347. doi: 10.2147/IJGM.S325980. eCollection 2021.
Type 2 diabetes mellitus (T2DM), a major risk factor of coronary heart disease, is associated with an approximately twofold increase in the risk of myocardial infarction (MI). We studied co-expressed genes to demonstrate relationships between DM and MI and revealed the potential biomarkers and therapeutic targets of T2DM-related MI.
DM and MI-related differentially expressed genes (DEGs) were identified by bioinformatic analysis, Gene Expression Omnibus (GEO) datasets GSE42148 and GSE61144 of MI patients, and the normal control and GSE26168 and GSE15932 of DM patients and normal controls, respectively. Further target prediction and network analysis method were used to detect protein-protein interaction (PPI) networks, gene ontology (GO) terms, and pathway enrichment of DEGs. Co-expressed DEGs of T2DM-related MI were analyzed as well.
We identified 210 upregulated and 127 downregulated DEGs in T2DM, as well as 264 upregulated and 242 downregulated DEGs in MI. Eighteen upregulated and four downregulated DEGs were identified as co-DEGs of T2DM and MI. Functional analysis revealed that T2DM-related DEGs were mostly enriched in the viral process and ubiquitin-mediated proteolysis, while MI-related DEGs were mostly enriched in protein phosphorylation and TNF signaling pathway. , , , , , , , and were recognized as the hub genes of the co-DEGs with acceptable diagnostic values in T2DM and MI datasets. Adenosine receptor agonist IB-MECA was predicted to be a potential drug for T2DM-related MI with the highest CMap connectivity score.
Our study identified that the co-DEGs of , , , , , , , and are significantly associated with novel biomarkers involved in T2DM-related MI. However, more experimental research and clinical trials are demanded to verify our results.
2型糖尿病（T2DM）是冠心病的主要危险因素，与心肌梗死（MI）风险增加约两倍相关。我们研究了共表达基因以证明糖尿病与心肌梗死之间的关系，并揭示了T2DM相关心肌梗死的潜在生物标志物和治疗靶点。
通过生物信息学分析、心肌梗死患者的基因表达综合数据库（GEO）数据集GSE42148和GSE61144以及正常对照，以及糖尿病患者和正常对照的GSE26168和GSE15932，分别鉴定出糖尿病和心肌梗死相关的差异表达基因（DEG）。进一步采用靶标预测和网络分析方法检测DEG的蛋白质-蛋白质相互作用（PPI）网络、基因本体（GO）术语和通路富集情况。还分析了T2DM相关心肌梗死的共表达DEG。
我们在T2DM中鉴定出210个上调和127个下调的DEG，在心肌梗死中鉴定出264个上调和242个下调的DEG。18个上调和4个下调的DEG被鉴定为T2DM和心肌梗死的共DEG。功能分析表明，T2DM相关的DEG大多富集于病毒过程和泛素介导的蛋白水解，而心肌梗死相关的DEG大多富集于蛋白质磷酸化和TNF信号通路。 、 、 、 、 、 、 和 被认为是共DEG的枢纽基因，在T2DM和心肌梗死数据集中具有可接受的诊断价值。腺苷受体激动剂IB-MECA被预测为T2DM相关心肌梗死的潜在药物，具有最高的CMap连接分数。
我们的研究确定， 、 、 、 、 、 、 和 的共DEG与T2DM相关心肌梗死中涉及的新型生物标志物显著相关。然而，需要更多的实验研究和临床试验来验证我们的结果。
