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基于生物信息学的急性心肌梗死免疫炎症相关生物标志物的鉴定

Identification of Immuno-Inflammation-Related Biomarkers for Acute Myocardial Infarction Based on Bioinformatics.

作者信息

You Hongjun, Dong Mengya

机构信息

Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, People's Republic of China.

出版信息

J Inflamm Res. 2023 Aug 7;16:3283-3302. doi: 10.2147/JIR.S421196. eCollection 2023.

Abstract

PURPOSE

Previous studies have confirmed that inflammation and immunity are involved in the pathogenesis of acute myocardial infarction (AMI). However, only few related genes are identified as biomarkers for the diagnosis and treatment of AMI.

PATIENTS AND METHODS

GSE48060 and GSE60993 datasets were retrieved from Gene Expression Omnibus. The differentially expressed immuno-inflammation-related genes (DEIIRGs) were obtained from GSE48060, and the biomarkers for AMI were screened and validated using the "Neuralnet" package and GSE60993 dataset. Further, the biomarker-based nomogram was constructed, and miRNAs, transcription factors (TFs), and potential drugs targeting the biomarkers were explored. Furthermore, immune infiltration analysis was analyzed in AMI. Finally, the biomarkers were verified by assessing their mRNA levels using real-time quantitative PCR (RT-qPCR).

RESULTS

First, eight biomarkers were screened via bioinformatics, and the artificial neural network model indicated a higher prediction accuracy for AMI even in the validation dataset. Nomogram had accurate forecasting ability for AMI as well. The TFs GTF2I, PHOX2B, RUNX1, and FOS targeting hsa-miR-1297 could regulate the expressions of and , and could effectively interact with melatonin and citalopram. RT-qPCR results for ADM, PI3, MMP9, NRG1 and CBLB were consistent with those of bioinformatic analysis.

CONCLUSION

In conclusion, eight key immuno-inflammation-related genes, namely, , and , may serve as the potential biomarkers for AMI, in which the downregulation of and upregulation of , and in AMI was detected for the first time, providing a new strategy for the diagnosis and treatment of AMI.

摘要

目的

先前的研究已证实炎症和免疫参与急性心肌梗死(AMI)的发病机制。然而,仅有少数相关基因被鉴定为AMI诊断和治疗的生物标志物。

患者与方法

从基因表达综合数据库(Gene Expression Omnibus)中检索GSE48060和GSE60993数据集。从GSE48060中获取差异表达的免疫炎症相关基因(DEIIRGs),并使用“Neuralnet”软件包和GSE60993数据集筛选和验证AMI的生物标志物。此外,构建基于生物标志物的列线图,并探索靶向这些生物标志物的微小RNA(miRNAs)、转录因子(TFs)和潜在药物。此外,对AMI进行免疫浸润分析。最后,通过实时定量聚合酶链反应(RT-qPCR)评估生物标志物的mRNA水平来验证这些生物标志物。

结果

首先,通过生物信息学筛选出8个生物标志物,人工神经网络模型显示即使在验证数据集中对AMI也具有较高的预测准确性。列线图对AMI也具有准确的预测能力。靶向hsa-miR-1297的TFs GTF2I、PHOX2B、RUNX1和FOS可调节[具体基因1]、[具体基因2]和[具体基因3]的表达,且[具体基因4]可与褪黑素和西酞普兰有效相互作用。ADM、PI3、MMP9、NRG1和CBLB的RT-qPCR结果与生物信息学分析结果一致。

结论

总之,8个关键的免疫炎症相关基因,即[具体基因1]、[具体基因2]、[具体基因3]、[具体基因4]、[具体基因5]、[具体基因6]、[具体基因7]和[具体基因8],可能作为AMI的潜在生物标志物,其中首次检测到AMI中[具体基因1]和[具体基因2]的下调以及[具体基因3]、[具体基因4]、[具体基因5]、[具体基因6]、[具体基因7]和[具体基因8]的上调,为AMI的诊断和治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49ef/10417757/518c93dd5648/JIR-16-3283-g0001.jpg

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