CEBPD may function as a molecular indicator of fibrotic severity and negative regulator of fibrosis in uterine leiomyoma through regulating EMT progression.

To investigate the expression pattern, diagnostic value, and molecular mechanism of CCAAT/enhancer-binding protein delta (CEBPD) in uterine leiomyoma (ULM)-associated fibrosis, and to identify novel diagnostic biomarkers and therapeutic targets for ULM. We analyzed transcriptional profiles of two independent ULM cohorts (GSE64763, GSE95101) to screen differentially expressed genes and enriched pathways. The diagnostic performance of CEBPD was evaluated via receiver operating characteristic (ROC) curve analysis. Single-cell RNA sequencing (scRNA-seq) data were used to map CEBPD's cellular distribution in the ULM microenvironment, with pseudotime and correlation analyses to explore its association with epithelial-mesenchymal transition (EMT) and fibrosis. Histological validation was performed using H&E and double immunofluorescence staining in clinical ULM specimens. CEBPD was significantly downregulated in ULM tissues, with enrichment in immune-related signaling pathways. It exhibited robust diagnostic accuracy for ULM, with area under the curve (AUC) values of 0.878 (95% CI: 0.783-0.973) and 0.858 (95% CI: 0.735-0.981) in the two cohorts. scRNA-seq identified 8 cell subsets in the ULM microenvironment, and CEBPD expression was dynamically and negatively correlated with key fibrotic mediators (COL1A1, COL1A2, COL3A1, all p < 0.001) and EMT-related factors (ZFP36, KLF2, NR4A1, all p < 0.001). Co-localization of CEBPD and T lymphocyte marker CD3E was confirmed in clinical specimens. CEBPD emerges as a potential prognostic biomarker for uterine fibroids. Mechanistically, its dynamic expression is strongly associated with the fibrotic cascade and inversely correlated with EMT progression as well as the expression of major extracellular matrix genes. These findings suggest that CEBPD may be a key regulatory factor in fibroid pathogenesis, offering a promising molecular target that warrants further functional validation in clinical management.