Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data.
Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data.
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DOI：
10.21037/tp-23-196
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发表时间：
2023-04-29
影响因子：
2
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中科院分区：
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癫痫是一种慢性疾病，其特征是由突然异常的神经元放电引起的短暂性脑功能障碍。近年来的研究表明，与炎症和先天免疫相关的通路在癫痫的发病机制中起着重要作用，提示免疫和炎症过程与癫痫的发生存在相互关系。然而，免疫相关机制尚未得到确切的了解，因此，本研究旨在探讨癫痫疾病的免疫相关机制，在分子水平上突出免疫细胞在癫痫中的作用，为癫痫患者提供治疗靶点。收集来自健康和癫痫个体的脑组织样品用于转录组测序以鉴定差异表达基因（DEG）和差异表达（DE）长编码RNA（lncRNA）。基于miRcode、starBase2.0、miRDB、miRTarBase、TargetScan和ENCORI数据库的相互作用，创建了lncRNA相关竞争性内源RNA（ceRNA）网络。基因本体论和基因分析的京都百科全书确定了ceRNA网络中的基因主要富集在免疫相关途径中。还进行了免疫相关ceRNA的免疫细胞浸润、筛选和蛋白质-蛋白质相互作用分析，以及免疫相关核心信使RNA（mRNA）与免疫细胞之间的相关性分析。获得9个枢纽基因（EGFR、GRB 2、KRAS、FOS、ESR 1、MAPK 1、MAPK 14、MAPK 8和PPARG）。此外，38个lncRNA、一个miRNA（hsa-miR-27 a-3 p）和一个mRNA（EGFR）构成最终的核心ceRNA网络。肥大细胞、浆细胞样树突状细胞和未成熟树突状细胞均与EGFR呈正相关，而分化簇56 dim自然杀伤细胞（CD 56 dim自然杀伤细胞）呈负相关。最后，我们采用癫痫小鼠模型来验证EGFR，这与疾病进展一致。总之，癫痫的病理生理学与EGFR相关。因此，EGFR可能是青少年局灶性癫痫的一种新的生物标志物，我们的研究结果为癫痫提供了有希望的治疗靶点。
Epilepsy is a chronic disease that is characterized by transient brain dysfunction caused by an abrupt abnormal neuronal discharge. Recent studies have indicated that the pathways related to inflammation and innate immunity play significant roles in the pathogenesis of epilepsy, suggesting an interrelationship between immunity and inflammatory processes and epilepsy. However, the immune-related mechanisms are still not precisely understood; therefore, this study aimed to explore the immune-related mechanisms in epilepsy disorders, highlight the role of immune cells at the molecular level in epilepsy, and provide therapeutic targets for patients with epilepsy. Brain tissue samples from healthy and epileptic individuals were collected for transcriptome sequencing to identify differentially expressed genes (DEGs) and differentially expressed (DE)-long coding RNAs (lncRNAs). Based on interactions from the miRcode, starBase2.0, miRDB, miRTarBase, TargetScan, and ENCORI databases, a lncRNA-associated competitive endogenous RNA (ceRNA) network was created. Gene ontology and the Kyoto encyclopedia of genes analyses established that the genes in the ceRNA network were mainly enriched in immune-related pathways. Immune cell infiltration, screening, and protein-protein interaction analyses of the immune-related ceRNAs, and correlation analysis between immune-related core messenger RNA (mRNA) and immune cells were also performed. Nine hub genes (EGFR, GRB2, KRAS, FOS, ESR1, MAPK1, MAPK14, MAPK8, and PPARG) were obtained. Also, 38 lncRNAs, one miRNA (hsa-miR-27a-3p), and one mRNA (EGFR) comprised the final core ceRNA network. Mast cells, plasmacytoid dendritic cells, and immature dendritic cells all showed positive correlations with EGFR, while Cluster of differentiation 56 dim natural killer cells (CD56dim natural killer cells) showed negative correlations. Finally, we employed an epilepsy mouse model to validate EGFR, which is consistent with disease progression. In conclusion, the pathophysiology of epilepsy was correlated with EGFR. Thus, EGFR could be a novel biomarker of juvenile focal epilepsies, and our findings provide promising therapeutic targets for epilepsy.
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影响因子：
5.1
作者：
Gong, Lina;Han, Yaru;Zhang, Chen
通讯作者：
Zhang, Chen
影响因子：
5.6
作者：
Granata T;Cross H;Theodore W;Avanzini G
通讯作者：
Avanzini G
影响因子：
3.8
作者：
Benedek G;Abed El Latif M;Miller K;Rivkin M;Ahmed Ramadhan Lasu A;P Riek L;Lako R;Edvardson S;Arbel-Alon S;Galun E;Levite M
通讯作者：
Levite M
影响因子：
4.5
作者：
通讯作者：
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影响因子：
8.3
作者：
Mattila, Olli S.;Strbian, Daniel;Lindsberg, Perttu J.
通讯作者：
Lindsberg, Perttu J.