Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction

Jiahe Wu; Huanhuan Cai; Zhe Lei; Chenze Li; Yushuang Hu; Tong Zhang; Haoyan Zhu; Yi Lu; Jianlei Cao; Xiaorong Hu

doi:10.3389/fcvm.2022.993592

Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction

Front Cardiovasc Med. 2022 Nov 3:9:993592. doi: 10.3389/fcvm.2022.993592. eCollection 2022.

Authors

Jiahe Wu^{1

2}, Huanhuan Cai^{1

2}, Zhe Lei^{1

2}, Chenze Li^{1

2}, Yushuang Hu^{1

2}, Tong Zhang^{1

2}, Haoyan Zhu^{1

2}, Yi Lu^{1

2}, Jianlei Cao^{1

2}, Xiaorong Hu^{1

2}

Affiliations

¹ Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.

Abstract

Background: Ferroptosis is a form of regulatory cell death (RCD) caused by iron-dependent lipid peroxidation. The role of ferroptosis in the process of acute myocardial infarction (AMI) is still unclear and requires further study. Therefore, it is helpful to identify ferroptosis related genes (FRGs) involved in AMI and explore their expression patterns and molecular mechanisms.

Methods: The AMI-related microarray datasets GSE66360 and GSE61144 were obtained using the Gene Expression Omnibus (GEO) online database. GO annotation, KEGG pathway enrichment analysis and Protein-protein interaction (PPI) analysis were performed for the common significant differential expression genes (CoDEGs) in these two datasets. The FRGs were obtained from the FerrDb V2 and the differentially expressed FRGs were used to identify potential biomarkers by receiver operating characteristic (ROC) analysis. The expression of these FRGs was verified using external dataset GSE60993 and GSE775. Finally, the expression of these FRGs was further verified in myocardial hypoxia model.

Results: A total of 131 CoDEGs were identified and these genes were mainly enriched in the pathways of "inflammatory response," "immune response," "plasma membrane," "receptor activity," "protein homodimerization activity," "calcium ion binding," "Phagosome," "Cytokine-cytokine receptor interaction," and "Toll-like receptor signaling pathway." The top 7 hub genes ITGAM, S100A12, S100A9, TLR2, TLR4, TLR8, and TREM1 were identified from the PPI network. 45 and 14 FRGs were identified in GSE66360 and GSE61144, respectively. FRGs ACSL1, ATG7, CAMKK2, GABARAPL1, KDM6B, LAMP2, PANX2, PGD, PTEN, SAT1, STAT3, TLR4, and ZFP36 were significantly differentially expressed in external dataset GSE60993 with AUC ≥ 0.7. Finally, ALOX5, CAMKK2, KDM6B, LAMP2, PTEN, PTGS2, and ULK1 were identified as biomarkers of AMI based on the time-gradient transcriptome dataset of AMI mice and the cellular hypoxia model.

Conclusion: In this study, based on the existing datasets, we identified differentially expressed FRGs in blood samples from patients with AMI and further validated these FRGs in the mouse time-gradient transcriptome dataset of AMI and the cellular hypoxia model. This study explored the expression pattern and molecular mechanism of FRGs in AMI, providing a basis for the accurate diagnosis of AMI and the selection of new therapeutic targets.

Keywords: ROC analysis; acute myocardial infarction; bioinformatics analysis; biomarker; ferroptosis.