Ferroptosis and Preeclampsia: Genetic Analysis of Potential Biomarkers and Therapeutic Targets

Abstract

Ferroptosis is the oxidative death of cells attributed to an imbalance in intracellular lipid reactive oxygen species metabolism, a reduction in cell antioxidant capacity, and an accumulation of membrane lipid peroxides. Trophoblast cells are a group of cells susceptible to ferroptosis. The ferroptosis of trophoblast cells has a major effect on the development of preeclampsia (PE), although the impact of ferroptosis-related genes (FRGs) on PE has not been well characterized. This study obtained PE-related information from the Gene Expression Omnibus database and FRGs from the FerrDb ferroptosis database. Seventeen PE-related differentially expressed ferroptosis-related genes (DE-FRGs) that were closely associated with cellular regulation and immune response were obtained. According to the results of a subsequent functional enrichment analysis, it was found that the above marker genes may impact PE by regulating immune response, amino acid metabolism, the cell cycle, and multiple pathways correlated with PE pathogenesis. Subsequently, we used LASSO and support vector machine recursive feature elimination algorithms to help identify GOT1, CFL1, FZD7, VDR, PARP6, TMSB4X, VCP, and ENO3 as marker genes from the 17 obtained genes. According to the results of single-sample gene set enrichment analysis (ssGSEA), the immune microenvironment of PE changed, possibly due to the GOT1 and TMSB4X genes. Furthermore, 23 drugs targeting one marker gene were determined. A constructed ceRNA network revealed a complicated regulatory link based on the eight marker genes. In this study, diagnostic potency was developed, and insight into the mechanism of PE was provided. In-depth research should be conducted before clinical application to evaluate the diagnostic value of DE-FRGs in PE.

Keywords: Bioinformatics; Diagnostic; Ferroptosis; Immune microenvironment; Placenta; Preeclampsia.