Development of immune-derived molecular markers for preeclampsia based on multiple machine learning algorithms

Preeclampsia (PE) is a major pregnancy-specific cardiovascular complication posing latent life-threatening risks to mothers and neonates. The contribution of immune dysregulation to PE is not fully understood, highlighting the need to explore molecular markers and their relationship with immune infiltration to potentially inform therapeutic strategies. We used bioinformatics tools to analyze gene expression data from the Gene Expression Omnibus (GEO) database using the GEOquery package in R. Differential expression analysis was performed using the DESeq2 and limma packages, followed by analysis of variance to identify immune-related differentially expressed genes (DEGs). Several machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), bagged trees, and random forest (RF), were used to select immune-related signaling genes closely associated with the occurrence of PE. Our analysis identified 34 immune source-related DEGs. Using the identified PE- and immune source-related genes, we constructed a diagnostic forecasting model employing several ML algorithms. We identified six types of statistically significant immune cells in patients with PE and discovered a strong relationship between biomarkers and immune cells. Moreover, the immune-derived hub genes for PE exhibited strong binding capabilities with drugs, such as alitretinoin, tretinoin, and acitretin. This study presents a robust prediction model for PE that integrates multiple machine learning-derived immune-related biomarkers. Our results indicate that these biomarkers may outperform previously reported molecular signatures in predicting PE and provide insights into the mechanisms underlying immune dysregulation in PE. Further validation in larger cohorts could lead to their clinical application in PE prediction and treatment.