Lu Feng, Mai Zifeng, Zhang Longfei, Luo Hao, Wang Lifeng, Li Shihong, Zhong Maolin
Department of Anesthesiology, The First Affiliated Hospital of Gannan Medical University, No. 128 Jinling Road, Ganzhou, Jiangxi, China.
Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, China.
Mol Neurobiol. 2025 Apr 16. doi: 10.1007/s12035-025-04931-4.
Spinal cord injury (SCI) often results in severe sensory, motor, and autonomic dysfunction, with limited treatment options due to complex underlying mechanisms. Disulfidptosis, a recently discovered form of cell death driven by disulfide bond accumulation, has been linked to various diseases, but its role in SCI remains unexplored. This study investigates the involvement of disulfidptosis-related genes (DRGs) in SCI to identify potential diagnostic markers and therapeutic targets. Using SCI datasets from the Gene Expression Omnibus (GEO), we conducted differential gene expression analysis, identifying key disulfidptosis-related differentially expressed genes (DRDEGs). Further analysis through gene set enrichment (GSEA) and Bayesian pathway enrichment highlighted significant involvement in pathways such as NF-κB, PI3K/Akt, and MAPK, with an emphasis on nephrin family interactions. Three core DRDEGs-HK2, Map3k8, and S100a6-were identified, and a diagnostic model built on these genes demonstrated strong predictive performance (AUC: 0.896 in training, 0.850 in validation). Additionally, real-time PCR (qRT-PCR) in an animal model validated the elevated expression of these DRDEGs in SCI samples. This research provides novel insights into disulfidptosis in SCI, suggesting these genes as promising targets for improved diagnostic and therapeutic strategies.
脊髓损伤（SCI）常导致严重的感觉、运动和自主神经功能障碍，由于其潜在机制复杂，治疗选择有限。二硫键堆积驱动的细胞死亡形式——二硫化物诱导细胞焦亡（Disulfidptosis），已被证实与多种疾病相关，但其在脊髓损伤中的作用尚不清楚。本研究旨在探讨二硫化物诱导细胞焦亡相关基因（DRGs）在脊髓损伤中的作用，以确定潜在的诊断标志物和治疗靶点。利用基因表达综合数据库（GEO）中的脊髓损伤数据集，我们进行了差异基因表达分析，确定了关键的二硫化物诱导细胞焦亡相关差异表达基因（DRDEGs）。通过基因集富集分析（GSEA）和贝叶斯通路富集分析进一步发现，这些基因显著参与了NF-κB、PI3K/Akt和MAPK等信号通路，尤其在nephrin家族相互作用中起重要作用。我们确定了三个核心DRDEGs——HK2、Map3k8和S100a6，并基于这些基因构建的诊断模型显示出强大的预测性能（训练集AUC：0.896，验证集AUC：0.850）。此外，动物模型中的实时荧光定量PCR（qRT-PCR）验证了这些DRDEGs在脊髓损伤样本中的表达上调。本研究为脊髓损伤中的二硫化物诱导细胞焦亡提供了新的见解，表明这些基因有望成为改善诊断和治疗策略的靶点。
