PANoptosis-related gene biomarkers in aortic dissection

Introduction

Programmed cell death of vascular smooth muscle cells (VSMCs) is critical in the pathogenesis of aortic dissection (AD), yet the role of PANoptosis—comprising pyroptosis, apoptosis, and necroptosis—remains unclear.

Methods

We utilized the GSE213740 single-cell sequencing dataset to assess PANoptosis levels in VSMCs. Datasets GSE153434 and GSE147026 were employed to identify differentially expressed genes (DEGs) and perform weighted gene co-expression network analysis. PANoptosis gene sets were sourced from the GSEA website, with GSE52093 serving as the validation cohort. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction analyses were conducted, along with assessments of upstream regulators and immune cell infiltration. Validation was performed on aortic tissues from AD patients and mouse models.

Results

The single-cell dataset revealed an increased PANoptosis score in VSMCs in AD. Nineteen PANoptosis-related DEGs (PANDEGs) were identified, contributing to VSMC differentiation, DNA damage response, and apoptosis. KEGG analysis highlighted the P53 and TGF-β pathways, with PANDEGs positively correlating with immune cell infiltration. Key PANDEGs GADD45B, CDKN1A, and SOD2 were validated, showing co-expression with α-SMA.

Conclusion

The increased PANoptosis score in VSMCs suggests that GADD45B, CDKN1A, and SOD2 play crucial roles in AD.