Feng Tianbao, Hu Jiating, Xie Mi, Shi Guodong, Wang Qi, Yao Jingyuan, Liu Xiaoqin
Department of Radiology, The Affiliated Hospital of Yan'an University, Yan'an, Shaanxi, China.
Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
PLoS One. 2025 Jul 15;20(7):e0328002. doi: 10.1371/journal.pone.0328002. eCollection 2025.
Spinal cord injury (SCI) is a debilitating neurological condition that severely impacts motor, sensory, and autonomic functions, leading to significant challenges in patient quality of life and imposing substantial economic burdens on society. PANoptosis is an emerging concept in programmed cell death that combines three key processes: pyroptosis, apoptosis, and necroptosis. Research has demonstrated the significant roles of apoptosis, necroptosis, and pyroptosis in the progression of SCI. As such, targeting PANoptosis-related genes may offer new therapeutic targets and clinically relevant treatment strategies. This study seeks to identify distinct molecular subtypes of SCI and potential drugs for its treatment, based on the mechanisms of PANoptosis. We acquired RNA sequencing data from the Gene Expression Omnibus (GEO) datasets GSE151371 and performed Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) analysis to delineate differential biological functions between SCI patients and healthy controls. We identified a total of 1138 significant differentially expressed genes (DEGs), comprising 431 downregulated and 707 upregulated genes. We intersected DEGs with PANoptosis gene sets and identified 23 common genes. 23 PANoptosis-related genes were subjected to functional enrichment analysis and PANoptosis scores calculation. PANoptosis score in SCI samples was significantly higher than in HC samples. Additionally, a protein-protein interaction (PPI) network was established to identify hub genes, and 8 machine learning algorithms were used to narrowed down hub genes. BMX and CASP5 were consistently identified across all algorithms. Immune cell infiltration analysis revealed significant correlations between BMX and several immune cell types, highlighting its involvement in the inflammatory response after SCI. Through additional ROC curve analysis, we confirmed the promising diagnostic potential of BMX, with an AUC value of 0.987. Moreover, we predicted potential therapeutic agents and key regulatory factors interacting with BMX. We performed single-gene GSEA analysis to explore the biological functions and pathways associated with BMX. Finally, we created a rat model of SCI to experimentally confirm the elevated expression of BMX in the SCI group by quantitative real-time PCR (qRT-PCR), western blot (WB) and immunohistochemistry (IHC). In conclusion, our findings provide valuable insights into the molecular mechanisms underlying SCI, highlighting BMX, a PANoptosis-related gene, as a potential therapeutic target. These results underscore the necessity for future studies to explore these targets in clinical applications.
脊髓损伤(SCI)是一种使人衰弱的神经疾病,严重影响运动、感觉和自主功能,给患者的生活质量带来重大挑战,并给社会带来巨大经济负担。PANoptosis是程序性细胞死亡中的一个新兴概念,它结合了三个关键过程:焦亡、凋亡和坏死性凋亡。研究表明,凋亡、坏死性凋亡和焦亡在SCI的进展中发挥着重要作用。因此,靶向与PANoptosis相关的基因可能会提供新的治疗靶点和具有临床相关性的治疗策略。本研究旨在基于PANoptosis的机制,识别SCI的不同分子亚型及其潜在的治疗药物。我们从基因表达综合数据库(GEO)数据集GSE151371中获取了RNA测序数据,并进行了基因集变异分析(GSVA)和基因集富集分析(GSEA),以描绘SCI患者与健康对照之间的差异生物学功能。我们共鉴定出1138个显著差异表达基因(DEG),包括431个下调基因和707个上调基因。我们将DEG与PANoptosis基因集进行交集分析,鉴定出23个共同基因。对23个与PANoptosis相关的基因进行了功能富集分析和PANoptosis评分计算。SCI样本中的PANoptosis评分显著高于健康对照样本中的评分。此外,建立了蛋白质-蛋白质相互作用(PPI)网络以识别枢纽基因,并使用8种机器学习算法缩小枢纽基因范围。在所有算法中均一致鉴定出BMX和CASP5。免疫细胞浸润分析显示BMX与几种免疫细胞类型之间存在显著相关性,突出了其在SCI后炎症反应中的作用。通过额外的ROC曲线分析,我们证实了BMX具有良好的诊断潜力,AUC值为0.987。此外,我们预测了与BMX相互作用的潜在治疗药物和关键调控因子。我们进行了单基因GSEA分析,以探索与BMX相关的生物学功能和途径。最后,我们创建了SCI大鼠模型,通过定量实时PCR(qRT-PCR)、蛋白质免疫印迹(WB)和免疫组织化学(IHC)实验证实了SCI组中BMX的表达升高。总之,我们的研究结果为SCI的分子机制提供了有价值的见解,突出了与PANoptosis相关的基因BMX作为潜在治疗靶点的地位。这些结果强调了未来研究在临床应用中探索这些靶点的必要性。
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