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

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 ADM and CBLB, and RORA 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, SH2D1B, ADM, PI3, MMP9, NRG1, CBLB, RORA, and FASLG, may serve as the potential biomarkers for AMI, in which the downregulation of CBLB and upregulation of ADM, PI3, and NRG1 in AMI was detected for the first time, providing a new strategy for the diagnosis and treatment of AMI.

Keywords:

• acute myocardial infarction
• immune-related gene
• inflammation-related gene
• biomarker
• nomogram

Data Sharing Statement

Publicly available datasets (GSE48060 and GSE60993) were analyzed in this study. These data can be found here: [GEO, https://www.ncbi.nlm.nih.gov/geo/].

Ethics Approval and Informed Consent

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Shaanxi Provincial People’s Hospital. Informed consent was obtained from all subjects involved in the study.

Consent for Publication

Written informed consent has been obtained from the patients to publish this paper.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest.