Department of Neurosurgery, The People's Hospital of Hengshui City, Hengshui, China.
Department of Endocrinology, The People's Hospital of Hengshui City, Hengshui, China.
World Neurosurg. 2023 Jun;174:e103-e117. doi: 10.1016/j.wneu.2023.03.004. Epub 2023 Mar 8.
Traumatic brain injury (TBI) is a major cause of neurological and psychological problems, especially long-term disability. The purpose of this article is to explore molecular mechanisms linking TBI and pyroptosis with the aim of providing a promising target for future therapeutic interventions.
GSE104687 microarray dataset was downloaded from the Gene Expression Omnibus database to obtain differential expressed genes. Meanwhile, pyroptosis-related genes were screened from GeneCards database, and the overlapped genes were considered as the pyroptosis-related genes in TBI. The immune infiltration analysis was conducted to quantify lymphocyte infiltration levels. Moreover, we researched the relevant microRNAs (miRNAs) and transcription factors and investigated the interactions and functions of miRNAs. In addition, the validation set and in vivo experiment further verified the expression of hub gene.
Altogether, we found 240 differential expressed genes in GSE104687 and 254 pyroptosis-related genes in the GeneCards database, and the overlapped gene was caspase 8 (CASP8). Immune Infiltration Analysis suggested the abundance of Tregs cells was significantly higher in TBI group. The NKT and CD8+ Tem were positively correlated with the expression levels of CASP8. The most significant term regarding CASP8 in Reactome pathways analysis was related to NF-kappaB. A total of 20 miRNAs and 25 transcription factors associated with CASP8 were obtained. After investigating the interactions and functions of miRNAs, the NF-kappaB-related signaling pathway was still enriched with a relatively low P-value. The validation set and in vivo experiment further verified the expression of CASP8.
Our study showed the potential role of CASP8 in pathogenesis of TBI, which may provide a new target for individualized therapy and drug development.
创伤性脑损伤（TBI）是神经和心理问题的主要原因，尤其是长期残疾。本文旨在探讨 TBI 与细胞焦亡之间的分子机制，以期为未来的治疗干预提供有希望的靶点。
从基因表达综合数据库（GEO）下载 GSE104687 微阵列数据集，以获得差异表达基因。同时，从基因卡片数据库筛选细胞焦亡相关基因，将重叠基因视为 TBI 中的细胞焦亡相关基因。进行免疫浸润分析以量化淋巴细胞浸润水平。此外，我们研究了相关的 microRNAs（miRNAs）和转录因子，并研究了 miRNAs 的相互作用和功能。另外，验证集和体内实验进一步验证了枢纽基因的表达。
总共在 GSE104687 中发现了 240 个差异表达基因，在基因卡片数据库中发现了 254 个细胞焦亡相关基因，重叠基因是半胱天冬酶 8（CASP8）。免疫浸润分析表明 TBI 组 Treg 细胞的丰度明显更高。NKT 和 CD8+ Tem 与 CASP8 的表达水平呈正相关。在 Reactome 途径分析中，与 CASP8 最显著的术语与 NF-kappaB 相关。共获得 20 个与 CASP8 相关的 miRNA 和 25 个转录因子。在研究了 miRNAs 的相互作用和功能后，NF-kappaB 相关信号通路仍然具有相对较低的 P 值。验证集和体内实验进一步验证了 CASP8 的表达。
我们的研究表明 CASP8 在 TBI 发病机制中具有潜在作用，这可能为个体化治疗和药物开发提供新的靶点。
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