BackgroundAs the precursor malignancy of endometrial cancer (EC), about 50% of endometrial complex atypical hyperplasia (CAH) will eventually progress to EC. Elucidating the underlying transformation mechanisms could aid in disease management.MethodsEC, CAH, reversed CAH and normal endometrium tissues were collected and sequenced to identify genes involved in the malignant transformation. CEBPB expression was then compared between endometrial CAH and normal endometrium. After evaluation of its effects on proliferation, apoptosis, EMT, migration and invasion by using primary culture, the promotion effects of CEBPB on endometrial CAH were further confirmed using RNA sequencing.ResultsBy integrating RNA sequencing data, CEBPB was identified as implicated in the transformation from endometrial CAH to EC. Endometrial CAH had overexpressed CEBPB compared with normal endometrium, but the expression decreased as the disease reversed. Primary cultures of CAH had enhanced proliferation, EMT, migration and invasion but reduced apoptosis compared with that of normal endometrium. Knockdown CEBPB in CAH primary cultures could suppress the proliferation, EMT, migration and invasion while increasing apoptosis, rendering the disease phenotype. Genes regulated by CEBPB were also significantly enriched in pathways related to the malignant transformation.ConclusionsCEBPB is involved in endometrial CAH and promotes the transformation from CAH to EC. CEBPB could potentially be exploited as a surrogate screening and surveillance biomarker for endometrial CAH at high cancerous risk, enabling better risk stratification and individualized treatment.