Guo Lei, Lv Jing, Huang Yun-Fei, Hao Ding-Jun, Liu Ji-Jun
Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Neural Regen Res. 2019 Jul;14(7):1262-1270. doi: 10.4103/1673-5374.251335.
Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury, which may affect the microenvironment of the damaged site. Microarray analysis provides a new opportunity for investigating diagnosis, treatment, and prognosis of spinal cord injury. However, differentially expressed genes are not consistent among studies, and many key genes and signaling pathways have not yet been accurately studied. GSE5296 was retrieved from the Gene Expression Omnibus DataSet. Differentially expressed genes were obtained using R/Bioconductor software (expression changed at least two-fold; P < 0.05). Database for Annotation, Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors. The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease. In total, this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5, 4, and 24 hours, and 3, 7, and 28 days after spinal cord injury. The number of downregulated genes was smaller than the number of upregulated genes at each time point. Database for Annotation, Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord. Additionally, expression levels of these inflammation-related genes were maintained for at least 28 days. Moreover, 399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes. Among the 10 upregulated differentially expressed genes with the highest degrees of distribution, six genes were transcription factors. Among these transcription factors, ATF3 showed the greatest change. ATF3 was upregulated within 30 minutes, and its expression levels remained high at 28 days after spinal cord injury. These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.
基因谱分析表明，脊髓损伤后基因表达和信号通路会发生显著变化，这可能会影响损伤部位的微环境。微阵列分析为研究脊髓损伤的诊断、治疗和预后提供了新的契机。然而，不同研究中差异表达基因并不一致，许多关键基因和信号通路尚未得到准确研究。从基因表达综合数据库中检索到GSE5296。使用R/Bioconductor软件获得差异表达基因（表达变化至少两倍；P<0.05）。利用注释、可视化和综合发现数据库对差异表达基因进行功能注释，并利用动物转录因子数据库预测潜在转录因子。将得到的转录调控蛋白相互作用网络进行映射，以筛选代表性基因并研究其对疾病的诊断和治疗价值。本研究共鉴定出脊髓损伤后0.5小时、4小时和24小时以及3天、7天和28天上调的109个基因和下调的30个基因。每个时间点下调基因的数量少于上调基因的数量。注释、可视化和综合发现数据库分析发现，损伤脊髓中许多炎症相关通路上调。此外，这些炎症相关基因的表达水平至少维持28天。此外，上调的差异表达基因的蛋白质-蛋白质相互作用网络显示出399种调控模式和77个节点。在分布度最高的10个上调差异表达基因中，有6个基因是转录因子。在这些转录因子中，ATF3变化最大。ATF3在30分钟内上调，脊髓损伤后28天其表达水平仍保持较高。通过生物信息学工具筛选出的这些关键基因可作为疾病诊断的生物标志物，并为确定治疗靶点提供参考。
