Single-Cell analysis Uncovers the Dynamic Process of EMT in Endometrial Cancer and the Core Roles of INHBA and POSTN in Regulating Tumor Malignant Phenotypes

Endometrial cancer (EC) incidence rises with aging and obesity epidemics. While early-stage EC has favorable outcomes, metastatic disease portends poor survival, necessitating biomarkers for metastasis prediction. Epithelial-mesenchymal transition (EMT) drives EC progression, but its dynamics and core regulators in clinical specimens remain uncharacterized.We performed single-cell RNA sequencing on 7 EC, integrated with bulk RNA-seq from 521 TCGA-UCEC cases. Cellular trajectories were reconstructed via pseudotime analysis. A specific 47 gene signature was derived by consensus non-negative matrix factorization. Core EMT regulators were functionally validated in vitro. We mapped a sequential EMT progression axis in clinical specimens, identifying a transitional hybrid E/M state. A specific 47-gene signature stratified patients into two groups with significantly divergent survival; functional validation pinpointed INHBA and POSTN as core EMT drivers, whose knockdown suppressed migration and invasion, reversed EMT, and impaired proliferation, with stage-dependent upregulation confirmed in advanced EC. This study defines INHBA and POSTN as central EMT regulators with prognostic and therapeutic potential, providing the first map of EMT dynamics in clinical EC specimens.