Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data

作者全名："Luo, Yujia; Xiao, Han; Chen, Hui; Gan, Hui; Zhang, Mi; Palahati, Ailiyaer; Duan, Yuhao; Zhai, Xuan"

作者地址："[Luo, Yujia; Xiao, Han; Chen, Hui; Gan, Hui; Zhang, Mi; Palahati, Ailiyaer; Duan, Yuhao; Zhai, Xuan] Chongqing Med Univ, Childrens Hosp,Minist Educ, China Int Sci & Technol Cooperat Base Child Dev &, Natl Clin Res Ctr Child Hlth & Disorders,Dept Neu, Chongqing, Peoples R China; [Luo, Yujia; Xiao, Han; Chen, Hui; Gan, Hui; Zhang, Mi; Palahati, Ailiyaer; Duan, Yuhao] Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China"

通信作者："Zhai, X (通讯作者)，Chongqing Med Univ, Childrens Hosp,Minist Educ, China Int Sci & Technol Cooperat Base Child Dev &, Natl Clin Res Ctr Child Hlth & Disorders,Dept Neu, Chongqing, Peoples R China."

来源：TRANSLATIONAL PEDIATRICS

ESI学科分类：　

WOS号：WOS:001033127400014

JCR分区：Q2

影响因子：1.5

年份：2023

卷号：12

期号：4

开始页：681

结束页：694

文献类型：Article

关键词：Transcriptome; immune-related genes; pathogenesis; competitive endogenous RNA (ceRNA); long non-coding RNA (lncRNA)

摘要："Background: 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. Methods: 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. Results: 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. Conclusions: 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."

基金机构：National Natural Science Foundation of China [81971217]; Scientific Research Project of the National Clinical Research Center of Child Health and Disorders

基金资助正文：This study was supported by the National Natural Science Foundation of China (No.81971217) and the Scientific Research Project of the National Clinical Research Center of Child Health and Disorders (No. NCRC-2019-GP-17).