Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Spinal cord injury (SCI) involves complex immune and inflammatory responses impacting nerve regeneration and functional recovery.
• Understanding the peripheral immune inflammatory response in SCI is crucial but remains limited.

Purpose of the Study:

• To investigate microRNA and mRNA expression profiles in the peripheral blood of SCI patients.
• To identify potential biomarkers for SCI diagnosis and therapeutic targets related to immune inflammation.

Main Methods:

• High-throughput sequencing of peripheral blood microRNA and analysis of GEO database mRNA profiles (GSE151371).
• Bioinformatic approaches including differential expression analysis, functional enrichment, weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE.
• Validation using quantitative polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curve analysis.
• Immune cell proportion analysis using CIBERSORT and construction of a small RNA-mRNA interaction network.

Main Results:

• Identified 54 differentially expressed microRNAs and 1656 differentially expressed genes.
• Found abnormal activation or inhibition of immune and inflammation-related pathways (e.g., neutrophil extracellular trap, T cell receptor, NF-κB).
• Identified and validated three potential SCI biomarkers: ANO10 (increased mRNA), BST1 (increased mRNA), and ZFP36L2 (decreased mRNA).
• Observed altered proportions of various immune cells (e.g., increased naïve B cells, monocytes, neutrophils; decreased CD8+ T cells, NK cells) in SCI patients compared to healthy subjects.
• Demonstrated close relationships between ANO10, BST1, ZFP36L2, and specific immune cell types.

Conclusions:

• The study highlights the significant role of peripheral immune inflammation in spinal cord injury.
• ANO10, BST1, and ZFP36L2 are identified as potential diagnostic biomarkers for spinal cord injury.
• Findings offer new avenues for developing immune-inflammatory treatment strategies for SCI.