Identification and Validation of Ferroptosis-Related Genes in Patients with Acute Spinal Cord Injury

Mol Neurobiol. 2023 Sep;60(9):5411-5425. doi: 10.1007/s12035-023-03423-7. Epub 2023 Jun 14.

Abstract

Ferroptosis plays crucial roles in the pathology of spinal cord injury (SCI). The purpose of this study was to identify differentially expressed ferroptosis-related genes (DE-FRGs) in human acute SCI by bioinformatics analysis and validate the hub DE-FRGs in non-SCI and SCI patients. The GSE151371 dataset was downloaded from the Gene Expression Omnibus and difference analysis was performed. The differentially expressed genes (DEGs) in GSE151371 overlapped with the ferroptosis-related genes (FRGs) obtained from the Ferroptosis Database. A total of 41 DE-FRGs were detected in 38 SCI samples and 10 healthy samples in GSE151371. Then, enrichment analyses of these DE-FRGs were performed for functional annotation. The GO enrichment results showed that upregulated DE-FRGs were mainly associated with reactive oxygen species and redox reactions, and the KEGG enrichment analysis indicated involvement in some diseases and ferroptosis pathways. Protein-protein interaction (PPI) analysis and lncRNA-miRNA-mRNA regulatory network were performed to explore the correlations between genes and regulatory mechanisms. The relationship between DE-FRGs and differentially expressed mitochondria-related genes (DE-MRGs) was also analyzed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the hub DE-FRGs in clinical blood samples from acute SCI patients and healthy controls. Consistent with the bioinformatics results, qRT-PCR of the clinical samples indicated similar expression levels of TLR4, STAT3, and HMOX1. This study identified DE-FRGs in blood samples from SCI patients, and the results could improve our understanding of the molecular mechanisms of ferroptosis in SCI. These candidate genes and pathways could be therapeutic targets for SCI.

Keywords: Bioinformatics; Ferroptosis; Quantitative real-time polymerase chain reaction; Spinal cord injury.

MeSH terms

  • Computational Biology
  • DNA, Mitochondrial
  • Databases, Factual
  • Ferroptosis* / genetics
  • Humans
  • MicroRNAs*

Substances

  • MicroRNAs
  • DNA, Mitochondrial