Wang Yongjie, Zhang Zilin, Gong Weiquan, Lv Zhenshan, Qi Jinwei, Han Song, Liu Boyuan, Song Aijun, Yang Zongyuan, Duan Longfei, Zhang Shaokun
Department of Spine Surgery, Center of Orthopedics, The First Hospital of Jilin University, Changchun 130021, China.
Department of Spine Surgery, Center of Orthopedics, The First Hospital of Jilin University, Changchun 130021, China; Jilin Engineering Research Center for Spine and Spinal Cord Injury, Changchun 130021, China.
Int Immunopharmacol. 2025 Mar 6;149:114220. doi: 10.1016/j.intimp.2025.114220. Epub 2025 Feb 9.
Spinal cord injury (SCI) is a severe condition affecting the central nervous system. It is marked by a high disability rate and potential for death. Research has demonstrated that programmed cell death (PCD) plays a significant role in the death of neuronal cells during SCI. The objective of our work was to illustrate the significant contribution of PCD genes in the progression of SCI.
SCI-related datasets GSE5296, GSE47681, and GSE189070 from the Gene Expression Omnibus database were comprehensively analyzed using bioinformatics methods. Common differentially expressed genes were validated by post-intersection screening with PCD genes. We constructed a gene prediction model using the least absolute shrinkage and selection operator and the random forest algorithm to further screen for characteristic genes. We also performed Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis and generated a protein-protein interaction network, analyzed immune cell infiltration, and predicted upstream miRNAs and transcription factors. In animal experiments, we performed immunofluorescence staining of mouse SCI regions to verify gene expression.
A total of five characteristic genes (Ctsd, Abca1, Cst7, Ctsb, and Cybb) were identified in our study and showed excellent diagnostic efficacy in predicting SCI progression (areas under the curve values of the five characteristic genes were 0.976 for Ctsd, 0.993 for Abca1, 0.995 of Cst7,0.986 of Ctsb, 0.959 of Cybb). These characterized genes were highly expressed at the site of SCI. Immune cell infiltration analysis revealed that multiple immune cells were involved in SCI progression.
We identified five PCD genes (Ctsd, Abca1, Cst7, Ctsb, and Cybb) associated with SCI. This study helps to reveal the pathophysiologic influences of these genes on SCI and provides important insight for the development of more effective treatments.
脊髓损伤（SCI）是一种影响中枢神经系统的严重病症。其特点是致残率高且有死亡风险。研究表明，程序性细胞死亡（PCD）在脊髓损伤期间神经元细胞死亡中起重要作用。我们研究的目的是阐明PCD基因在脊髓损伤进展中的重要作用。
使用生物信息学方法对来自基因表达综合数据库的与脊髓损伤相关的数据集GSE5296、GSE47681和GSE189070进行综合分析。通过与PCD基因进行交集后筛选来验证常见的差异表达基因。我们使用最小绝对收缩和选择算子以及随机森林算法构建基因预测模型，以进一步筛选特征基因。我们还进行了基因本体功能富集分析和京都基因与基因组百科全书通路分析，并生成了蛋白质-蛋白质相互作用网络，分析了免疫细胞浸润，并预测了上游miRNA和转录因子。在动物实验中，我们对小鼠脊髓损伤区域进行免疫荧光染色以验证基因表达。
我们的研究共鉴定出五个特征基因（组织蛋白酶D（Ctsd）、三磷酸腺苷结合盒转运体A1（Abca1）、半胱氨酸蛋白酶7（Cst7）、组织蛋白酶B（Ctsb）和细胞色素b（Cybb）），它们在预测脊髓损伤进展方面显示出优异的诊断效能（五个特征基因的曲线下面积值分别为：Ctsd为0.976，Abca1为0.993，Cst7为0.995，Ctsb为0.986，Cybb为0.959）。这些特征基因在脊髓损伤部位高度表达。免疫细胞浸润分析表明，多种免疫细胞参与脊髓损伤的进展。
我们鉴定出五个与脊髓损伤相关的PCD基因（Ctsd、Abca1、Cst7、Ctsb和Cybb）。本研究有助于揭示这些基因对脊髓损伤的病理生理影响，并为开发更有效的治疗方法提供重要见解。
