Ma Yawen, Liu Yunhui, Ruan Xuelei, Liu Xiaobai, Zheng Jian, Teng Hao, Shao Lianqi, Yang Chunqing, Wang Di, Xue Yixue
Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, China.
Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
Front Genet. 2021 Mar 30;12:646436. doi: 10.3389/fgene.2021.646436. eCollection 2021.
Traumatic brain injury (TBI) is a brain function change caused by external forces, which is one of the main causes of death and disability worldwide. The aim of this study was to identify early diagnostic markers and potential therapeutic targets for TBI. Differences between TBI and controls in GSE89866 and GSE104687 were analyzed. The two groups of differentially expressed genes (DEGs) were combined for coexpression analysis, and the modules of interest were performed using enrichment analysis. Hub genes were identified by calculating area under curve (AUC) values of module genes, PPI network analysis, and functional similarity. Finally, the difference in immune cell infiltration between TBI and control was calculated by ssGSEA. A total of 4,817 DEGs were identified in GSE89866 and 1,329 DEGs in GSE104687. They were clustered into nine modules. The genes of modules 1, 4, and 7 had the most crosstalk and were identified as important modules. Enrichment analysis revealed that they were mainly associated with neurodevelopment and immune inflammation. In the PPI network constructed by genes with top 50 AUC values in module genes, we identified the top 10 genes with the greatest connectivity. Among them, down-regulated RPL27, RPS4X, RPL23A, RPS15A, and RPL7A had similar functions and were identified as hub genes. In addition, DC and Tem were significantly up-regulated and down-regulated between TBI and control, respectively. We found that hub genes may have a diagnostic role for TBI. Molecular dysregulation mechanisms of TBI are associated with neurological and immune inflammation. These results may provide new ideas for the diagnosis and treatment of TBI.
创伤性脑损伤（TBI）是由外力引起的脑功能改变，是全球范围内死亡和残疾的主要原因之一。本研究的目的是确定TBI的早期诊断标志物和潜在治疗靶点。分析了GSE89866和GSE104687中TBI与对照组之间的差异。将两组差异表达基因（DEG）进行共表达分析，并对感兴趣的模块进行富集分析。通过计算模块基因的曲线下面积（AUC）值、蛋白质-蛋白质相互作用（PPI）网络分析和功能相似性来鉴定枢纽基因。最后，通过单样本基因集富集分析（ssGSEA）计算TBI与对照组之间免疫细胞浸润的差异。在GSE89866中总共鉴定出4817个DEG，在GSE104687中鉴定出1329个DEG。它们被聚类成九个模块。模块1、4和7的基因具有最多的相互作用，被确定为重要模块。富集分析表明，它们主要与神经发育和免疫炎症相关。在由模块基因中AUC值排名前50的基因构建的PPI网络中，我们鉴定出连接性最强的前10个基因。其中，下调的核糖体蛋白L27（RPL27）、核糖体蛋白S4X（RPS4X）、核糖体蛋白L23A（RPL23A）、核糖体蛋白S15A（RPS15A）和核糖体蛋白L7A（RPL7A）具有相似的功能，被确定为枢纽基因。此外，树突状细胞（DC）和效应性记忆T细胞（Tem）在TBI组和对照组之间分别显著上调和下调。我们发现枢纽基因可能对TBI具有诊断作用。TBI的分子失调机制与神经学和免疫炎症相关。这些结果可能为TBI的诊断和治疗提供新思路。
