Journal of Inflammation Research (May 2022)
Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data
Abstract
Yunqi Hou,1,* Zhen Chen,2,* Liping Wang,3 Yingxin Deng,1 Genglong Liu,4 Yongfen Zhou,1 Haiqin Shi,1 Xiangqun Shi,1 Qianhua Jiang2 1Department of Neurology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China; 2Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 570102, People’s Republic of China; 4Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, 510095, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunqi Hou, Department of Neurology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China, Email [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: epilepsy, immune-related genes, immune infiltration, Th1/Th2 signatures, CCR
