Comprehensive Analysis of Key Endoplasmic Reticulum Stress-Related Genes and Immune Infiltrates in Stanford Type A Aortic Dissection.

Abstract

Background: Type A aortic dissection is a fatal disease. However, the role of endoplasmic reticulum stress-related genes (ERSRGs) in type A aortic dissection has not yet been fully clarified.

Methods: Differentially expressed genes in the aorta of type A aortic dissection patients were analyzed based on the GSE52093 database. The ERSRGs were downloaded from the GeneCards website. Functional enrichment analysis and protein-protein interaction analysis were performed on the acquired differentially expressed ERSRGs. The mRNA expression of the 5 top key differentially expressed ERSRGs was further explored in GSE153434 and clinical samples. Immune infiltration correlation analysis was performed on the validated key genes. Finally, we constructed regulatory networks of transcription factors, miRNAs, and chemicals.

Results: Twelve differentially expressed ERSRGs were identified, of which 8 genes were downregulated and 4 genes were upregulated. GeneMANIA was adopted to analyze these genes and their interacting proteins, and the results showed that the main function was calcium ion transport. Four key genes, ACTC1, CASQ2, SPP1, and REEP1, were validated in GSE153434 and clinical samples. The area under the ROC curve values for ACTC1, CASQ2, SPP1, and REEP1 were 0.92, 0.96, 0.89, and 1.00, respectively. ACTC1 and REEP1 correlated with multiple immune cells. Many transcription factors, microRNAs, and chemicals were identified with the potential to regulate these 4 key genes.

Conclusion: In this study, we identified 12 differentially expressed ERSRGs by analyzing the Gene Expression Omnibus database. Four key genes may influence the development of type A aortic dissection by regulating endoplasmic reticulum stress. These results expand our understanding of type A aortic dissection, and the 4 key genes are expected to be diagnostic markers and potential therapeutic targets.