👤 Thirunavukkarasu Velusamy

Preeclampsia (PE), a severe hypertensive disorder of pregnancy, is associated with circadian rhythm disruption, but the underlying placental molecular networks remain poorly understood. This study aimed to identify key hub genes, regulatory pathways, and novel biomarkers at the intersection of Early-Onset PE (EOPE) and the placental circadian clock. The placental transcriptomic dataset GSE114691 (20 EOPE vs. 20 gestational age-matched preterm controls) was analyzed to identify differentially expressed circadian genes (DECGs). Hub genes were prioritized via protein-protein interaction (PPI) networks. Hub gene expression was validated using effect size (Cohen's d) analysis, and diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) curve analysis. An upstream TF-miRNA co-regulatory network and drug-gene interactions were also analyzed. This pipeline identified 33 DECGs and 10 central hub genes (TGFB1, SPP1, ENG, CD63, SNAI1, GPT2, APLN, EZR, NTRK2, and GLUD1), all significantly dysregulated in EOPE. Crucially, analysis of the core clock machinery revealed a specific uncoupling of the regulatory feedback loop. ROC analysis revealed exceptional diagnostic potential. Notably, NTRK2 emerged as a novel, near-perfect classifier (Area Under the Curve [AUC] = 0.99), outperforming the established marker ENG (AUC = 0.97). Upstream analysis identified key transcription factors (FOXC1, GATA2), and drug-gene analysis revealed clinically relevant interactions between TGFB1 and the chronotherapeutic agents melatonin and aspirin. This study provides a systems-level map of the disrupted placental circadian network in EOPE. Our findings suggest that circadian misalignment is a central feature of placental pathology, offering a molecular rationale for developing novel chronotherapeutic strategies. Show less