Exploration of N7-methylguanosine and immune-related biomarkers in Acute Aortic Dissection by combining bulk RNA-seq sequencing data and single-cell RNA sequencing

Purpose: Acute aortic dissection (AAD) is a life-threatening cardiovascular disease with high morbidity and mortality. Increasing evidence suggests that N7-methylguanosine (m7G) modification and immune dysregulation are involved in AAD, but the underlying mechanisms remain unclear. This study aimed to identify m7G-and immune-related biomarkers and explore their roles in AAD. Methods: Public bulk RNA-seq datasets were analyzed to identify differentially expressed genes (DEGs). m7G-related genes and immune-related genes were collected from the literature. Weighted gene co-expression network analysis and machine learning were used to screen biomarkers. Gene set enrichment analysis was performed to investigate their functional pathways. Single-cell RNA sequencing was used to identify key cell populations, and RT-qPCR was conducted to validate biomarker expression in clinical samples. Results: A total of 1,597 DEGs, 3,466 key module genes, and 101 candidate genes were identified. GlmBoost+RF was selected as the optimal model combination, and five biomarkers, including ESM1, HMOX1, SHC1, SLC11A1, and TNFRSF10D, were finally identified. These biomarkers were mainly enriched in growth factor receptor-and second messenger-related signaling pathways. Single-cell analysis indicated that macrophages were the key cell population associated with biomarker expression. RT-qPCR confirmed significant upregulation of ESM1, HMOX1, and SHC1, while SLC11A1 and TNFRSF10D showed nonsignificant upward trends in AAD tissues. Conclusion: ESM1, HMOX1, SHC1, SLC11A1, and TNFRSF10D may serve as promising diagnostic biomarkers for AAD, and macrophage-centered immune dysregulation may contribute to AAD pathogenesis.