Using weighted gene co-expression network analysis to identify key genes related to preeclampsia.

INTRODUCTION: The pathogenesis of preeclampsia remains unclear, highlighting the need for the creation of dependable biomarkers. This study aimed to pinpoint genetic risk factors linked to preeclampsia through the utilization of weighted gene co-expression network analysis (WGCNA). METHODS: A gene expression profile dataset from the placentas of patients with preeclampsia was acquired from the Gene Expression Omnibus (GEO) database and employed as a discovery cohort to construct a WGCNA network. Functional enrichment analysis, pathway analysis, and the construction of protein-protein interaction (PPI) networks were performed on core genes within these modules to pinpoint hub genes. The GSE25906 dataset was utilized as a validation cohort to evaluate the diagnostic significance of the hub genes. Immunohistochemistry assays were employed to validate the protein expression levels of these genes in placental tissues from both preeclampsia and control groups. RESULTS: Through WGCNA, 33 co-expression modules were identified, with 4 modules significantly associated with multiple clinical traits (≥3). Among these, 75 core genes were highlighted, predominantly enriched in pathways related to the adaptive immune response and platelet activation. Notably, TYROBP, PLEK, LCP2, HCK, and ITGAM emerged as hub genes with high PPI network scores and strong diagnostic potential, all prominently associated with immunity-related pathways. Protein expression analysis revealed that these genes were downregulated in placental tissues from preeclampsia patients compared to healthy controls. DISCUSSIONS: TYROBP, PLEK, LCP2, HCK, and ITGAM are closely linked to preeclampsia and hold promise as potential biomarkers for its diagnosis and for advancing the understanding of its pathogenesis.