Differential expressions of endoplasmic reticulum stress-associated genes in aortic dissection and their correlation with immune cell infiltration
10.12122/j.issn.1673-4254.2024.05.07
- VernacularTitle:内质网应激相关基因在主动脉夹层疾病中的差异性表达及与免疫浸润的相关性
- Author:
Wei ZHOU
1
;
Jun NIE
;
Jia HU
;
Yizhi JIANG
;
Dafa ZHANG
Author Information
1. 皖南医学院第一附属医院 心胸外科,安徽 芜湖 241002
- Keywords:
aortic dissection;
endoplasmic reticulum stress;
immune cell infiltration;
bioinformatics
- From:
Journal of Southern Medical University
2024;44(5):859-866
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore differentially expressed endoplasmic reticulum stress-associated genes(ERSAGs)in aortic dissection(AD)and their correlations with immune cell infiltration to identify new therapeutic targets for AD.Methods Two AD mRNA expression datasets(GSE190635 and GSE98770)were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software.ERSAGs dataset was downloaded from GeneCards website,and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes.Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software.Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting AGER mRNA expression using qRT-PCR,and the upstream transcriptional factors,miRNAs,and chemicals targeting AGER were analyzed using the TRRUST database and NetworkAnalyst database.Results Bioinformatic analysis suggested significant differential expression of AGER in AD,which interacted with 20 proteins involved in pattern recognition receptor signaling pathway,positive regulation of DNA-binding transcription factor activity,myeloid leukocyte migration,leukocyte migration,and regulation of the I-κB kinase/NF-κB signaling.In AD,AGER expression level was positively correlated with Treg cell abundance(r=0.59,P<0.05).The results of qRT-PCR demonstrated significantly lower expression of AGER mRNA in AD than in non-AD patients(1.00±0.30 vs 1.76±0.68,P<0.05).ROC curve analysis showed that at the cut-off value of 1.335,AGER had an AUC of 0.86(95%CI:0.67-1.00,P=0.0073)for predicting AD.Three transcriptional factors,3 miRNAs,and 27 chemicals were predicted in the AGER regulatory network.Conclusion AGER is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.
