This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach, while also predicting potential traditional Chinese medicines (TCMs) targeting these genes. The findings might offer a foundation for understanding ferroptosis mechanisms in psoriasis and exploring TCM-based therapeutic strategies. To begin, we retrieved gene expression profile data from psoriasis patients and healthy controls from the Gene Expression Omnibus (GEO) database, followed by data normalization. Ferroptosis-associated differentially expressed genes (Fer-DEGs) were identified using the FerrDb database. Subsequent GO and KEGG enrichment analyses provided insights into the biological functions and signaling pathways of these Fer-DEGs. Core Fer-DEGs were identified using machine learning algorithms, and their expression levels were further validated with an external dataset to evaluate diagnostic potential. Additionally, the symMap database facilitated the reverse prediction of TCMs targeting these key signature genes. The analysis identified 265 significant Fer-DEGs. GO enrichment indicated their involvement in diverse biological processes, while KEGG analysis highlighted their roles in various pathways, including ferroptosis, autophagy, cancer, infection, and metabolism, as well as PI3K-Akt, FoxO, mTOR, and HIF-1 signaling pathways. Machine learning pinpointed nine core psoriasis-related Fer-DEGs: PRKAA2, ANO6, POR, PTEN, MAPK8, ZFAS1, ADAM23, TMBIM4, and PARP14, all demonstrating strong diagnostic performance. Predicted TCMs primarily included those with heat-clearing, detoxifying, blood-activating, stasis-resolving, and phlegm-resolving properties. In conclusion, our study suggested that PRKAA2, ANO6, POR, PTEN, MAPK8, ZFAS1, ADAM23, TMBIM4, and PARP14 were key players in the ferroptosis pathway in psoriasis. TCMs with properties such as heat-clearing, blood activation, and phlegm resolution might hold promise for anti-ferroptosis interventions in psoriasis treatment.
>
>