Screening and identification of hub genes for ischemic cardiomyopathy and construction and validation of a clinical prognosis model using bioinformatics analysis

Jing Wang; Liying Tang; Yuzhi Bai; Xia Zhao; Tian Tian; Christos G Mihos; Eva Maria Javier Delmo; Pei Li

doi:10.21037/jtd-23-1722

Screening and identification of hub genes for ischemic cardiomyopathy and construction and validation of a clinical prognosis model using bioinformatics analysis

J Thorac Dis. 2024 Apr 30;16(4):2421-2431. doi: 10.21037/jtd-23-1722. Epub 2024 Apr 2.

Authors

Jing Wang¹, Liying Tang¹, Yuzhi Bai¹, Xia Zhao¹, Tian Tian¹, Christos G Mihos², Eva Maria Javier Delmo³, Pei Li¹

Affiliations

¹ Department of General Practice, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
² Echocardiography Laboratory, Columbia University Irving Medical Center, Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA.
³ Charité Research Organization, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Abstract

Background: Myocardial ischemia and hypoxia may result in myocardial cell necrosis, scar formation, and hyperplasia. We aim to explore the differentially expressed genes (DEGs) in ischemic cardiomyopathy (ICM), construct and identify a clinical prognosis model using bioinformatics methods, so as to screen potential biomarkers of ICM to provide a basis for the early diagnosis and treatment of ICM.

Methods: Based on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, R language was used to screen DEGs in healthy myocardial (n=5) and ICM myocardial tissues (n=12). DEGs were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI). Receiver operating characteristic (ROC) curves were drawn to verify the target genes.

Results: A total of 259 genes with significantly changed fold change (FC) values were obtained through conditional screening, including up-regulated genes and down-regulated genes. The first two hub genes [interleukin-6 (IL-6) and Ras homologous gene family member A (RHOA)] with the largest degree value among the above up-regulated and down-regulated genes were selected and their expression values were combined in the gene chip to draw the ROC curve based on the pROC package of R language. The area under the ROC curve (AUC) values of IL-6 and RHOA were 0.956 and 0.995, respectively. The expression levels of Sqstm1, Nos2, IL-6, RHOA, and Zfp36 genes in the ICM group are lower than those in the blank control group and the difference was statistically significant (P<0.05). RHOA and Stat3 were identified as the key genes controlling the occurrence and development of ICM.

Conclusions: ICM is closely related to the changes of extracellular matrix (ECM) and oxidoreductase activity. The IL-6 and RHOA are expected to become potential targets for ICM treatment.

Keywords: Ischemic cardiomyopathy (ICM); bioinformatics analysis; differentially expressed genes (DEGs); long non-coding RNA (lncRNA).