Tan Jiahong, Zhao Lin, Wang Daoqi, Wu Xiaodie, Bi Yongxiang, Wang Hanying, Ma Na, Yang Dehong, Dong Wei, Zhang Jie
Department of Obstetrics and Gynecology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, 650032, People's Republic of China.
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No.374 Dianmian Avenue, Kunming, 650101, People's Republic of China.
BMC Cancer. 2025 Jun 3;25(1):989. doi: 10.1186/s12885-025-14394-4.
As 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.
EC, 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.
By 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.
CEBPB 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.
作为子宫内膜癌（EC）的前驱恶性肿瘤，约50%的子宫内膜复杂性非典型增生（CAH）最终会进展为EC。阐明其潜在的转化机制有助于疾病管理。
收集EC、CAH、逆转的CAH和正常子宫内膜组织并进行测序，以鉴定参与恶性转化的基因。然后比较子宫内膜CAH和正常子宫内膜中CEBPB的表达。通过原代培养评估其对增殖、凋亡、上皮-间质转化（EMT）、迁移和侵袭的影响后，利用RNA测序进一步证实CEBPB对子宫内膜CAH的促进作用。
通过整合RNA测序数据，确定CEBPB与子宫内膜CAH向EC的转化有关。与正常子宫内膜相比，子宫内膜CAH中CEBPB过表达，但随着疾病逆转其表达降低。与正常子宫内膜的原代培养相比，CAH的原代培养增殖、EMT、迁移和侵袭增强，但凋亡减少。在CAH原代培养中敲低CEBPB可抑制增殖、EMT、迁移和侵袭，同时增加凋亡，呈现疾病表型。受CEBPB调控的基因在与恶性转化相关的通路中也显著富集。
CEBPB参与子宫内膜CAH并促进CAH向EC的转化。CEBPB有可能被用作高癌变风险子宫内膜CAH的替代筛查和监测生物标志物，从而实现更好的风险分层和个体化治疗。
