Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy

Kai Huang; Kun Mei; Jiahao Duan; Ruting Wang; Chun Yang; Bin Wang; Renjun Gu; Ling Yang

doi:10.3389/fcvm.2023.1078290

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy

Front Cardiovasc Med. 2023 Feb 21:10:1078290. doi: 10.3389/fcvm.2023.1078290. eCollection 2023.

Authors

Kai Huang¹, Kun Mei², Jiahao Duan¹, Ruting Wang¹, Chun Yang³, Bin Wang², Renjun Gu^{4

5}, Ling Yang¹

Affiliations

¹ Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
² Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
³ Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁴ Nanjing University of Chinese Medicine, Nanjing, China.
⁵ School of Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

Background: Cardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM.

Methods: We downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR.

Results: Overall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray.

Conclusion: Our study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.

Keywords: GEO; bioinformatics analysis; ferroptosis; immune microenvironment; ischemic cardiomyopathy.