Bioinformatics Analysis of Ferroptosis-Related Driver Genes in Stanford Type A Aortic Dissection

Stanford type A aortic dissection (TAAD) is a life-threatening cardiovascular condition associated with high mortality. Ferroptosis has been implicated in TAAD pathogenesis, but comprehensive analyses and experimental validation of ferroptosis-related driver genes (FRDGs) remain limited. This study systematically investigated FRDGs in TAAD using bioinformatics and experimental approaches. Differentially expressed ferroptosis-related driver genes (DEFRDGs) were identified by integrating the GSE153434 dataset with the FerrDb database. Functional enrichment analysis was subsequently performed, followed by the construction of a protein–protein interaction (PPI) network, assessment of immune cell infiltration, and prediction of potential miRNA interactions. Candidate hub genes were then validated using an independent cohort (GSE52093) and clinical tissue samples, with their diagnostic value evaluated via receiver operating characteristic (ROC) curve analysis and their protein expression confirmed by immunohistochemistry. We identified 25 DEFRDGs (17 upregulated, 8 downregulated) enriched in oxidative stress, iron binding, and ferroptosis/HIF-1 signaling pathways. Six hub genes (HIF1A, IL6, TIMP1, SAT1, HMOX1, LPCAT3) were significantly upregulated in validation cohorts, five genes (HIF1A, TIMP1, SAT1, HMOX1, LPCAT3) achieved an area under the curve (AUC) of 1.000, while IL6 also exhibited high diagnostic accuracy (AUC = 0.914). Fibroblast infiltration was elevated in TAAD tissues. Further miRNA interaction prediction revealed the potential involvement of miRNAs, such as miR-138-5p, miR-18b-5p, miR-199a-5p, miR-185-5p, miR-506-3p and miR-4644. Immunohistochemistry confirmed increased protein expression of HIF1A, SAT1, and LPCAT3. These three genes emerge as key ferroptosis-related drivers in TAAD. Their consistent upregulation and strong diagnostic performance support ferroptosis as a potential therapeutic target and provide a basis for mechanism-focused interventions.