Bioinformatics analysis of differentially expressed genes related to ischemia and hypoxia in spinal cord injury and construction of miRNA-mRNA or mRNA-transcription factor interaction network

Abstract

Background

Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration.

Methods

The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration.

Results

There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration.

Conclusion

Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration.

Keywords:

• Spinal cord injury
• ischemia and hypoxia
• immune infiltration
• integrated bioinformatics
• biomarkers

Author contributions

LJZ was the main designer of this study. LJZ, NG, ZBZ, SPZ, and JZ performed the experiments and analyzed the data. LJZ, NG, ZBZ, XL, and JZ drafted the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by Shaanxi Provincial Youth Fund (No. 2022JQ-935).