Blood transcriptome analysis: Ferroptosis and potential inflammatory pathways in post-traumatic stress disorder

BACKGROUND: Transcriptome-wide analysis of peripheral blood in post-traumatic stress disorder (PTSD) indicates widespread changes in immune-related pathways and function. Ferroptosis, an iron-dependent regulated cell death, is closely related to oxidative stress. However, little is known as to whether ferroptosis plays a role in PTSD. METHODS: We conducted a comprehensive analysis of combined data from six independent peripheral blood transcriptional studies in the Gene Expression Omnibus (GEO) database, covering PTSD and control individuals. Differentially expressed genes (DEGs) were extracted by comparing PTSD patients with control individuals, from which 29 ferroptosis-related genes (FRGs) were cross-matched and obtained. The weighted gene co-expression network analysis (WGCNA), the Extreme Gradient Boosting (XGBoost) model with Bayesian Optimization, and the least absolute shrinkage and selection operator (LASSO) Cox regression were utilized to construct a PTSD prediction model. Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT revealed the disturbed immunologic state in PTSD high-risk patients. RESULTS: Three crucial FRGs (ACSL4, ACO1, and GSS) were identified and used to establish a predictive model of PTSD. The receiver operating characteristic (ROC) curve verifies its risk prediction ability. Remarkably, ssGSEA and CIBERSORT demonstrated changes in cellular immunity and antigen presentation depending on the FRGs model. CONCLUSION: These findings collectively provide evidence that ferroptosis may change immune status in PTSD and be related to the occurrence of PTSD, which may help delineate mechanisms and discover treatment biomarkers for PTSD.