Abstract
Endometrial cancer (EC) exhibits increasing incidence and mortality, necessitating novel prognostic biomarkers and therapeutic targets. This study systematically investigates EPHB2 as a potential biomarker through comprehensive bioinformatics (TIMER 2.0, Human Protein Atlas, Xanadu Academic Online, Sento Academic Online, TCGA, GeneMANIA, GSEA, BEST database, and SCAR database) and experimental analyses (si-EPHB2 and OE-EPHB2 RL95-2 cell models with RT-qPCR, western blot, CCK-8, wound healing, Transwell, and TUNEL assays). Our findings demonstrate that EPHB2 is significantly overexpressed in EC, correlating with advanced pathological grade, histological type, and poor prognosis, while its high expression activates PI3K/AKT/MAPK signaling and promotes proliferation, migration, invasion, and suppresses apoptosis; conversely, EPHB2 knockdown exhibits opposite effects, revealing its critical role in EC progression through immune modulation and oncogenic signaling activation, thereby establishing EPHB2 as a promising therapeutic target for EC treatment.