Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from coronary artery disease

J Cell Mol Med. 2022 Apr;26(8):2177-2190. doi: 10.1111/jcmm.17239. Epub 2022 Feb 13.

Abstract

Ferroptosis plays a key role in the death of cells including cardiomyocytes, and it is related to a variety of cardiac diseases. However, the role of ferroptosis-related genes (FRGs) in coronary artery disease (CAD) is not well characterized. We downloaded CAD-related information and FRGs from the gene expression omnibus (GEO) database and Ferroptosis Database (FerrDb) respectively. A total of 10 CAD-related DE-FRGs were obtained, which were closely linked to autophagy regulation and immune response. Subsequently, CA9, CBS, CEBPG, HSPB1, SLC1A4, STMN1 and TRIB3 among the 10 DE-FRGs were identified as marker genes by LASSO and SVM-RFE algorithms, which had tolerable diagnostic capabilities. Subsequent functional enrichment analysis showed that these marker genes may play a corresponding role in CAD by participating in the regulation of immune response, amino acid metabolism, cell cycle and multiple pathways related to the pathogenesis of CAD. Furthermore, a total of 58 drugs targeting 7 marker genes had been obtained. On the contrary, the ceRNA network revealed a complex regulatory relationship based on the marker genes. Also, CIBERSORT analysis showed that the changes in the immune microenvironment of CAD patients may be related to CBS, HSPB1 and CEBPG. We developed a diagnostic potency and provided an insight for exploring the mechanism for CAD. Before clinical application, further research is needed to test its diagnostic value for CAD.

Keywords: bioinformatics; cardiac; coronary artery disease; diagnostic; ferroptosis; immune microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System ASC
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Coronary Artery Disease* / genetics
  • Ferroptosis* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans

Substances

  • Amino Acid Transport System ASC
  • Biomarkers, Tumor
  • SLC1A4 protein, human