Development and Validation of a Diagnostic Model Based on Hypoxia-Related Genes in Myocardial Infarction

Abstract

Purpose

Myocardial infarction (MI) is a common cardiovascular disease, and its underlying pathological mechanism remains unclear. We aimed to develop a diagnostic model to distinguish different subtypes of MI.

Patients and Methods

The gene expression profiles of MI from the GEO database and hypoxia-related genes (HRGs) from MSigDB were downloaded. Then, the different MI subtypes based on HRGs were identified with unsupervised clustering. The difference of expression patterns and hypoxic-immune status among different subtypes of MI were investigated. The diagnostic model to distinguish the different subtypes of MI was developed and validated.

Results

Based on HRGs, MI samples were divided into two subtypes, cluster A and cluster B. A total of 211 genes showed significant changes in expression between the two subtypes. Cluster A was characterized by high hypoxia status and low immunity status. Based on weighted gene co-expression network analysis, ROC analysis and LASSO regression algorithm, 5 genes were identified as potential diagnostic markers. Finally, a diagnostic model based on these 5 genes was established, which can distinguish the two subtypes well.

Conclusion

The five hub genes, including ANKRD36, HLTF, KIF3A, OXCT1 and VPS13A, may be associated with the different subtypes of MI.

Keywords:

• myocardial infarction
• hypoxia
• immune
• diagnostic model

Abbreviations

MI, Myocardial infarction; HRG, Hypoxia-related genes; IME, Immune microenvironment; WGCNA, Weighted gene co-expression network analysis; GS, Gene significance; MM, module membership; AUC, area under the ROC curve; RT-qPCR, Real-time qPCR; EMT, epithelial-to-mesenchymal transition; ANKRD36, Ankyrin repeat domain 36; HLTF, Helicase like transcription factor; KIF3A, kinesin family member 3A; OXCT1, 3-oxoacid CoA-transferase 1.

Data Sharing Statement

The data supporting the conclusions of this article are included within the article.

Ethics Approval and Informed Consent

Approval was obtained from the ethics committee of The Second Affiliated Hospital of Shandong First Medical University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for Publication

The subjects gave written informed consent for the publication of any associated data and accompanying images.

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

All authors declare that they have no conflicts of interest in this work.

Additional information

Funding

There is no funding to report.