Identification of Potential Ferroptosis-Related Biomarkers and Immune Infiltration in Human Coronary Artery Atherosclerosis

Objective: Ferroptosis is a specific subtype of programmed cell death, which plays an essential role in the immune-associated disease, atherosclerosis (AS). The purpose of this study was to identify potential ferroptosis-related gene biomarkers and its association with immune infiltration characteristics in atherosclerosis with bioinformatics methods. Methods: Differentially expressed genes (DEGs) between AS and control groups were screened from GSE40231, analyzed for functional enrichment and then intersected with ferroptosis-related genes. Then, a random forest model was constructed based on these differentially expressed ferroptosis-related genes (DE-FRGs) and validated with dataset GSE132651. The performance of the models was evaluated with the area under receiver operating characteristic curves (AUC). Finally, we analyzed the correlation between DEFRGs above and the characteristics of immune infiltration via CIBERSORT method. Results: Six DE-FRGs (IL6, ANGPTL7, CDKN1A, AKR1C3, NOX4 and VLDLR) were detected based on dataset of GSE40231. Furthermore, a random forest model was constructed based on them with a compelling diagnostic performance of AUC = 0.8974 in the validation dataset GSE132651. In addition, the proportion of follicular helper T (Tfh) cells was significantly higher in AS group (P < 0.001). And we found significant correlation relationship between Tfh and expression level of ANGPTL7 (R = 0.35, P < 0.01), CDKN1A (R = 0.4, P < 0.0001), AKR1C3 (R = 0.64, P < 0.0001), NOX4 (R = 0.32, P < 0.01) and VLDLR (R = -0.43, P < 0.0001). Conclusion: This study identified 6 DE-FRGs and validated a predicted model for the early prediction of AS, which also proved the close relationship between ferroptosis and immunity in the pathogenesis of AS.