Yang Haikun, Zhang Zhengping, Liu Haochang, Zhong Yaoxiang, Pan Ru, Zheng Dan, Li Lvyang, Yu Lie
Meizhou People's Hospital, Meizhou, Guangdong, China.
J Obstet Gynaecol. 2025 Dec;45(1):2551729. doi: 10.1080/01443615.2025.2551729. Epub 2025 Sep 13.
Although most cases of endometrial cancer (EC) are diagnosed at an early stage with favourable outcomes, the prognosis for advanced or recurrent disease remains poor, highlighting the need for novel therapeutic targets. This study aimed to examine the correlation between Cyclin B1 (CCNB1) and Cyclin B2 (CCNB2) expression and disease severity in EC through bioinformatics analysis.
Common differentially expressed genes were identified in two EC cohorts from the Gene Expression Omnibus. A protein-protein interaction (PPI) network was constructed to identify hub genes. Aberrant expression of the hub genes was validated in external datasets. Their prognostic values were evaluated in a cohort from The Cancer Genome Atlas (TCGA). Knockdown of the hub genes was conducted to explore their functions in the malignant behaviour of EC cells .
CCNB1 and CCNB2 were identified as the top 2 hub genes in the PPI network. High CCNB1/CCNB2 expression was significantly associated with shorter survival in EC patients. Overexpression of CCNB1/CCNB2 in endometrial tumour tissue was validated in public datasets. In TCGA cohort, high expression of CCNB1/CCNB2 correlated with greater disease severity and predicted poor prognosis. In addition, high expression of CCNB1/CCNB2 was strongly associated with immune cell infiltration, as well as increased expression of immune checkpoint genes and mismatch repair genes. Furthermore, knockdown of CCNB1/CCNB2 significantly suppressed the proliferation, migration, and invasion of HEC-1 and Ishikawa cells .
CCNB1 and CCNB2 may serve as potential prognostic markers and therapeutic targets for the management of EC.
尽管大多数子宫内膜癌（EC）病例在早期被诊断出来且预后良好，但晚期或复发性疾病的预后仍然很差，这凸显了对新型治疗靶点的需求。本研究旨在通过生物信息学分析探讨细胞周期蛋白B1（CCNB1）和细胞周期蛋白B2（CCNB2）表达与EC疾病严重程度之间的相关性。
在来自基因表达综合数据库的两个EC队列中鉴定出常见的差异表达基因。构建蛋白质-蛋白质相互作用（PPI）网络以识别枢纽基因。在外部数据集中验证枢纽基因的异常表达。在来自癌症基因组图谱（TCGA）的队列中评估它们的预后价值。对枢纽基因进行敲低以探索它们在EC细胞恶性行为中的功能。
CCNB1和CCNB2被确定为PPI网络中的前2个枢纽基因。CCNB1/CCNB2高表达与EC患者较短的生存期显著相关。子宫内膜肿瘤组织中CCNB1/CCNB2的过表达在公共数据集中得到验证。在TCGA队列中，CCNB1/CCNB2的高表达与更高的疾病严重程度相关，并预测预后不良。此外，CCNB1/CCNB2的高表达与免疫细胞浸润以及免疫检查点基因和错配修复基因的表达增加密切相关。此外，敲低CCNB1/CCNB2显著抑制了HEC-1和Ishikawa细胞的增殖、迁移和侵袭。
CCNB1和CCNB2可能作为EC管理的潜在预后标志物和治疗靶点。
