Identification and validation of key biomarkers associated with immune and oxidative stress for preeclampsia by WGCNA and machine learning.

Background: Preeclampsia (PE), a major obstetric disorder marked by dysfunction in both placental and maternal vascular systems, continues to pose critical challenges in global maternal healthcare. This multisystem pregnancy complication contributes significantly to adverse perinatal outcomes and remains a leading cause of pregnancy-related morbidity worldwide. However, the available treatment options at present remain restricted. Our investigation employs an integrative bioinformatics approach to elucidate critical molecular signatures linked to the interplay between immunological dysregulation and oxidative stress mechanisms in PE pathogenesis. Methods: In this study, we sourced the dataset from the GEO database with the aim of pinpointing differentially expressed genes (DEGs) between PE samples and control samples. Genes associated with oxidative stress were procured from the Genecards database. Next, we employed a comprehensive approach. This involved integrating WGCNA, GO and KEGG pathway analyses, constructing PPI networks, applying machine learning algorithms, performing gene GSEA, and conducting immune infiltration analysis to identify the key hub genes related to oxidative stress. Diagnostic potential of candidate biomarkers was quantitatively assessed through ROC curve modeling. Additionally, we constructed a miRNA - gene regulatory network for the identified diagnostic genes and predicted potential candidate drugs. In the final step, we validated the significant hub gene using independent external datasets, the hypoxia model of the HTR-8/SVneo cell line, and human placental tissue samples. Results: At last, leptin (LEP) was identified as a core gene through screening and was found to be upregulated. The results of quantitative real-time polymerase chain reaction (qRT -PCR) and immunohistochemistry validation were consistent with those obtained from the datasets. KEGG analysis revealed that LEP was significantly enriched in "allograft rejection," "antigen processing," "ECM receptor interaction" and "graft Conclusion: Through an integrated analytical framework employing WGCNA coupled with three distinct machine learning-driven phenotypic classification models, we discovered a pivotal regulatory gene. This gene has the potential to act as a novel diagnostic biomarker for PE. Moreover, it can be considered as a promising target for drug development related to PE. Notably, it shows a strong correlation with the immune microenvironment, suggesting its crucial role in the complex pathophysiological processes underlying PE.