Integrative transcriptomic analysis of WNT/TGFβ-driven EMT pathways and drug-gene interaction networks in epithelial ovarian cancer

Background Epithelial ovarian cancer (EOC) remains a lethal malignancy, and epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance. Robust EMT-centered biomarkers in EOC are still lacking. We aimed to identify consensus EMT-related mRNA-miRNA signatures and drug-gene interactions across independent cohorts. Methods Three mRNA and one miRNA GEO datasets were analyzed. Differentially expressed genes (DEGs) were identified with limma and combined meta-analytically; consensus DEGs were directionally concordant with FDR <0.05. EMT involvement was evaluated using Hallmark EMT enrichment and correlations with EMTome-derived epithelial and mesenchymal scores in TCGA-OV. Functional enrichment, protein–protein interaction networks, hub genes, Human Protein Atlas validation, drug–gene interactions, and miRNA prediction and validation were integrated. Results We identified 528 consensus DEGs (131 up-regulated, 397 down-regulated) in EOC versus normal ovary. Up-regulated genes were enriched for EMT, extracellular matrix organization, and WNT/TGFβ/BMP signaling, whereas down-regulated genes involved signal transduction and cell-cell communication. Seventeen EMT-related genes, including NT5E, VIM, GAS1, and WNT5A, showed strong mesenchymal associations. Ten hub genes (AURKA, BIRC5, CDK1, EZH2, HMMR, IQGAP3, BCL2, DCN, NT5E, PGR) were consistently dysregulated, associated with poorer survival, and supported by protein-level differences. Integration with miRNA data highlighted ten EMT-related miRNAs, several with good diagnostic performance (AUC ≥0.80). Eight clinically relevant drug-gene pairs, including alisertib (AURKA) and venetoclax (BCL2), were prioritized. Conclusions This EMT-focused integrative analysis defines coherent mRNA-miRNA-drug axes in EOC. The identified EMT-regulatory modules provide candidate diagnostic and prognostic biomarkers and pathway-based therapeutic hypotheses that warrant validation in independent cohorts and functional models.

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