Exploration of Hub Genes and Immune Cell Infiltration Characteristics Associated With Spinal Cord Injury in Mice

Journal of Inflammation Research, 2025 · DOI: https://doi.org/10.2147/JIR.S499402 · Published: February 20, 2025

Simple Explanation

Spinal cord injury (SCI) is a serious disease caused by direct or indirect external forces on the spinal cord. In addition to the devastating impact of the primary injury, secondary injury is a huge obstacle to the recovery of neurological function. Immune cell infiltration and inflammatory cytokine release driven by multiple causes after SCI amplifies the secondary damage and impedes neurological recovery. Therefore, an in-depth understanding of the molecular mechanisms and immune cell infiltration associated with the development of secondary injury after SCI is critical for identifying novel therapeutic targets for neurological recovery. In this study, we screened the differential genes. Moreover, we conducted the weighted correlation network analysis (WGCNA) to screen out the candidate key genes, and obtained the most relevant genes to spinal cord injury according to least absolute shrinkage and selection operator (LASSO) and Receiver Operating Characteristic Curve (ROC) algorithms.

Study Duration

Not specified

Participants

BALB/c male mice (20–24 g, 6–8 weeks)

Evidence Level

Level Not specified, Animal study

Key Findings

1
A total of 522 DEGs were filtered. Enrichment analysis of their biological functions and pathways yielded the most closely related results for inflammatory response, regulation of cytokine production, neutrophil chemotaxis and degranulation, angiogenesis, cell death, TNF signaling pathway, and osteoclast differentiation.
2
Four Hub genes (2010004M13Rik, Cdkn1c, Nox4, and Gpr101) were obtained by analysis using the LASSO algorithm and validated by qRT-PCR.
3
The infiltration of M0 and M2 macrophages, T Cells CD4 Follicular, and DC activated was assessed by immune infiltration analysis and was found to be associated with SCI.

Research Summary

In the present study, we statistically analyzed the DEGs between SCI and normal tissue in the GSE5296 and GSE47681 datasets to obtain DEGs. The exploration of the relevance of differential genetic, biological processes, and signaling pathways revealed that DEGs were mainly enriched in the inflammatory response, regulation of cytokine production, neutrophil chemotaxis and degranulation, angiogenesis, and cell death. To further explore the Hub genes associated with spinal cord injury and the promotion of neurological recovery, we crossed the highly correlated genes screened by WGCNA with differential genes to obtain crossover genes that are both differential and correlated. Subsequently, 4 hub genes, 2010004M13Rik, Cdkn1c, Nox4, and Gpr101, were obtained utilizing the LASSO algorithm. Since immune cell infiltration is crucial to the development of SCI and the recovery of neurological function, we used the CIBERSORT algorithm to calculate the difference in immune cell i DC Actived, M0 macrophages, M2 macrophages, and T Cells CD4 Follicular in the injured tissue.

Practical Implications

Identification of Therapeutic Targets

The identification of hub genes (2010004M13Rik, Cdkn1c, Nox4, and Gpr101) provides potential therapeutic targets for improving neurological recovery after SCI.

Understanding Immune Cell Roles

Clarifying the roles of specific immune cells, such as M0 and M2 macrophages, T Cells CD4 Follicular, and DC activated, can help in developing immunotherapeutic strategies.

Precision Medicine Approaches

The study provides more precise biomarkers (Cdkn1c, Nox4, Gpr101, etc.) for clinical diagnosis and treatment, which promotes the development of precision medicine.

Study Limitations

1
The roles of the characteristic genes and immune cells in spinal cord injury need to be explored by further experiments.
2
Detailed studies on the role of 2010004M13Rik have not yet been reported.
3
Not specified

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