Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data.
Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data.
复制标题
DOI：
10.2147/jir.s360743
复制
发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
癫痫包括一组异质性脑部疾病，约占世界人口的1%。越来越多的证据表明，免疫系统在癫痫发生中起着关键作用。然而，免疫相关的机制仍然没有得到准确的理解。筛选三个癫痫数据集（GSE 16969、GSE 32534和GSE 143272）以获得差异表达的免疫相关基因（DEIRGs）。构建随机森林（RF）和蛋白质相互作用（PPI）网络来识别核心基因。另一个数据集（GSE 31718）和60个临床样本通过定量实时聚合酶链反应（qRT-PCR）用于验证核心基因。用CIBERSORTx工具和单样本基因集富集分析（ssGSEA）进行免疫细胞浸润评分。进行基因集变异分析（GSVA）和ssGSEA以确定在正常和癫痫期间显著富集的途径。通过Pearson相关性分析评价了中枢基因、免疫细胞和富集的分子途径之间的相关性。基于RF和PPI，4个DEIRGs（CSF 1 R、IL 6 R、TLR 2和TNFRSF 1A）被鉴定为枢纽基因。qRT-PCR的结果证实，与对照样品相比，癫痫样品中CSF 1 R、IL 6 R、TLR 2和TNFRSF 1A的表达水平更高。通过CIBERSORTx的免疫浸润分析显示，癫痫患者的免疫特征明显更丰富，特别是T细胞亚群。值得注意的是，ssGSEA发现Th 1特征在正常组织中更丰富;而Th 2特征在癫痫组织中更丰富。基于多转录组数据，细胞因子-细胞因子受体相互作用（CCR）在癫痫中显著富集。此外，枢纽基因与多转录组数据中的Th 1/Th 2特征评分和CCR富集评分显著相关。4种IRGs（CSF 1 R、IL 6 R、TLR 2和TNFRSF 1A）与癫痫的发病密切相关，可能通过影响CCR和Th 1/Th 2平衡参与癫痫的发生。我们的数据为癫痫的发病机制和有前途的治疗靶点提供了令人信服的见解。
Epilepsy encompasses a group of heterogeneous brain diseases that afflict about 1% of the world’s population. Accumulating evidence shows that the immune system plays a key role in epileptogenesis. Nevertheless, the immune-related mechanisms remain not been precisely understood. Three epilepsy datasets (GSE16969, GSE32534 and GSE143272) were screened to obtain differentially expressed immune-related genes (DEIRGs). Random forest (RF) and protein–protein interaction (PPI) network were constructed to identify core genes. Another dataset (GSE31718) and 60 clinical samples via quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to validate core genes. Immune cell infiltration score was performed with CIBERSORTx tools and single-sample gene set enrichment analysis (ssGSEA). Gene set variation analysis (GSVA) and ssGSEA were conducted to determine the pathways that are significantly enriched during normal and epilepsy. The correlation between hub genes, immune cells, and enriched molecular pathways was evaluated by Pearson correlation analysis. Based on RF and PPI, 4 DEIRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were identified as hub genes. Results of qRT-PCR validated that higher expression levels of CSF1R, IL6R, TLR2, and TNFRSF1A in epilepsy samples compared to control sample. Immune infiltration analysis by CIBERSORTx displayed immune signatures that are significantly richer in epilepsy, T cell subsets in particular. Notably, ssGSEA found that Th1 signatures were more abundant in normal tissues; yet Th2 signatures were more abundant in epilepsy tissues. Cytokine cytokine receptor interaction (CCR) was significantly enriched in epilepsy based on multi-transcriptome data. Additionally, hub genes were significantly correlated with score of Th1/Th2 signatures and enrichment score of CCR in multi-transcriptome data. Four IRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were closely correlated pathogenesis of epilepsy, which may be by impacting CCR and the balance of Th1/Th2 signatures involved in the occurrence of epilepsy. Our data offer compelling insights into the pathogenesis and promising therapeutic targets for epilepsy.