Integrated analysis of the diagnostic value and mechanism of action of the senescence-associated secretory phenotype in thoracic aortic aneurysm relying on bulk RNA-Seq and scRNA-Seq

Background Thoracic aortic aneurysm (TAA) eventually causes aortic intima rupture, and the senescence-associated secretory phenotype (SASP) has been found to promote TAA. Thus, identifying TAA early via SASP-related genes (SASP-RGs) is highly significant. Methods Differential analysis was performed on TAA datasets from GEO; SASP-RGs were expanded via weighted gene co-expression network analysis. Candidate key genes were obtained by combining these two analyses with protein-protein interaction, then identified via least absolute shrinkage and selection operator and expression verification. A nomogram was built using key genes, and immune cell infiltration in TAA was examined. Meanwhile, pathway enrichment and regulatory networks of key genes were explored. Key TAA-related cells in single-cell datasets and key gene expression in them were determined, with key gene expression validated in clinical samples. Results Among 36 candidates, CR1 and F13A1 were key genes; the nomogram had good diagnostic value. In TAA, infiltration of immune cells like macrophages and natural killer cells increased, showing positive correlation with key genes. Key genes were associated with the "chemokine signaling pathway" and regulated by transcription factors (e.g., SCL, SOX2). Macrophages were key cells; F13A1 expression fluctuated during macrophage development. Key gene expression was verified by PCR in clinical samples. Conclusion SASP-RGs play important roles in TAA and have diagnostic value, providing a basis for TAA early diagnosis and prevention.