Identification of feature autophagy-related genes in patients with acute myocardial infarction based on bioinformatics analyses.

Yajuan Du,Enfa Zhao,Yushun Zhang

doi:10.1042/bsr20200790

Abstract

Objective: To identify feature autophagy-related genes (ARGs) in patients with acute myocardial infarction (AMI) and further investigate their value in the diagnosis of AMI.Methods: Gene microarray expression data of AMI peripheral blood samples were downloaded from the GSE66360 dataset. The data were randomly classified into a discovery cohort (21 AMI patients and 22 healthy controls) and a validation cohort (28 AMI patients and 28 healthy controls). Differentially expressed ARGs between patients with AMI and healthy controls in the discovery cohort were identified using a statistical software package. Feature ARGs were screened based on support vector machine-recursive feature elimination (SVM-RFE), and an SVM classifier was constructed. Receiver operating characteristic (ROC) analysis was used to investigate the predictive value of the classifier, which was further verified in an independent external cohort.Results: A total of seven genes were identified based on SVM-RFE. The SVM classifier had an excellent discrimination ability in both the discovery cohort (area under the curve [AUC] = 0.968) and the validation cohort (AUC = 0.992), which was further confirmed in the GSE48060 dataset (AUC = 0.963). Furthermore, the SVM classifier showed outstanding discrimination between AMI patients with and without recurrent events in the independent external cohort (AUC = 0.992). The identified genes are mainly involved in the cellular response to autophagy, macroautophagy, apoptosis, and the FoxO signaling pathway.Conclusion: Our study identified feature ARGs and indicated their potential roles in AMI diagnosis to improve our understanding of the molecular mechanism underlying the occurrence of AMI.

Highlights

Acute myocardial infarction (AMI), known as acute heart attack in a clinical background of acute myocardial ischemia, is induced by the sudden blockade or occlusion of a major coronary artery branch, resulting in ischemia or infarction of cardiomyocytes [1]
To validate the feature autophagy-related gene (ARG) expression levels, the identified genes were selected for validation using the validation cohort
Using the recursive feature elimination (RFE) method, the feature genes in AMI samples were identified, which allowed the AMI samples to be distinguished from the control samples

Summary

Introduction

Acute myocardial infarction (AMI), known as acute heart attack in a clinical background of acute myocardial ischemia, is induced by the sudden blockade or occlusion of a major coronary artery branch, resulting in ischemia or infarction of cardiomyocytes [1]. The current diagnostic approaches for the evaluation of AMI generally comprise a physical examination, a surface electrocardiogram (ECG), and blood testing for gold standard cardiac biomarkers, such as cTnI/T and CKMB. These biomarkers have been criticized for their lack of sufficient specificity and sensitivity [3]. Classic risk factors, such as smoking, hypertension, high serum cholesterol, hypercholesterolemia, diabetes mellitus, and obesity, fail to fully explain the risks of morbidity and mortality from AMI. Previous studies have reported that patients with coronary heart disease often lack common risk factors; more than 20% of patients have no commonly accepted risk factors and 40% have only

Methods

Results

Conclusion