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<p>Spinal cord injury (SCI) profoundly impairs patients’ quality of life and imposes a substantial economic burden on society, often resulting in irreversible neurological deficits. To investigate the involvement of mitophagy-related genes (MRGs) in SCI, the GSE151371 dataset, comprising 38 SCI samples and 10 healthy control samples from the Gene Expression Omnibus (GEO) database, was analyzed. Key genes linking mitophagy to SCI pathogenesis were identified through an integrative approach combining differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning. A total of 1138 differentially expressed genes (DEGs) were identified between SCI patients and healthy controls (HC), among which 31 overlapping signature genes were shared between MRGs and WGCNA-derived module genes. Functional enrichment analysis revealed that these genes were mainly involved in biological processes related to neurotransmission and membrane dynamics. Machine learning–based feature selection identified seven hub genes, of which EXOSC4 was the only candidate consistently validated in the independent GSE45006 dataset. Immune infiltration analysis further demonstrated a pro-inflammatory microenvironment in SCI, characterized by increased neutrophil and macrophage infiltration. Single-cell RNA sequencing analysis using the GSE162610 dataset showed that <i>Exosc4</i> exhibited the highest mean expression in macrophage and endothelial cell populations. Moreover, quantitative PCR, Western blotting, and immunofluorescence analyses confirmed that EXOSC4 expression was significantly upregulated in SCI tissues. Collectively, these findings suggest that EXOSC4 may play an important role in SCI pathophysiology and has potential value as a diagnostic biomarker and therapeutic target. Despite limitations, including a relatively small sample size and the absence of clinical validation, this study highlights the significance of mitophagy-related gene regulation in SCI and provides a foundation for future studies aimed at validating EXOSC4 in larger cohorts and exploring its therapeutic relevance.</p>

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Upregulation of the Mitophagy-Related Gene EXOSC4 Is Associated with Immune Dysregulation in Spinal Cord Injury

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Xiaoqin Liu,
  • MengFan Li,
  • Jiating Hu,
  • PanFeng Fang,
  • Yuxin Ma,
  • Ziyu Guo,
  • Hongqiang Wang,
  • Chao Xu

摘要

Spinal cord injury (SCI) profoundly impairs patients’ quality of life and imposes a substantial economic burden on society, often resulting in irreversible neurological deficits. To investigate the involvement of mitophagy-related genes (MRGs) in SCI, the GSE151371 dataset, comprising 38 SCI samples and 10 healthy control samples from the Gene Expression Omnibus (GEO) database, was analyzed. Key genes linking mitophagy to SCI pathogenesis were identified through an integrative approach combining differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning. A total of 1138 differentially expressed genes (DEGs) were identified between SCI patients and healthy controls (HC), among which 31 overlapping signature genes were shared between MRGs and WGCNA-derived module genes. Functional enrichment analysis revealed that these genes were mainly involved in biological processes related to neurotransmission and membrane dynamics. Machine learning–based feature selection identified seven hub genes, of which EXOSC4 was the only candidate consistently validated in the independent GSE45006 dataset. Immune infiltration analysis further demonstrated a pro-inflammatory microenvironment in SCI, characterized by increased neutrophil and macrophage infiltration. Single-cell RNA sequencing analysis using the GSE162610 dataset showed that Exosc4 exhibited the highest mean expression in macrophage and endothelial cell populations. Moreover, quantitative PCR, Western blotting, and immunofluorescence analyses confirmed that EXOSC4 expression was significantly upregulated in SCI tissues. Collectively, these findings suggest that EXOSC4 may play an important role in SCI pathophysiology and has potential value as a diagnostic biomarker and therapeutic target. Despite limitations, including a relatively small sample size and the absence of clinical validation, this study highlights the significance of mitophagy-related gene regulation in SCI and provides a foundation for future studies aimed at validating EXOSC4 in larger cohorts and exploring its therapeutic relevance.