Integrated bioinformatic and experimental study links cyclin B1/B2 to poor prognosis and immune infiltration in endometrial cancer

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 <i>in vitro</i>. 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 <i>in vitro</i>. CCNB1 and CCNB2 may serve as potential prognostic markers and therapeutic targets for the management of EC. Endometrial cancer is a common cancer originating in the uterus lining. This study identified two genes, cyclin B1 and cyclin B2, as significantly more active in cancer tissue than in normal tissue. Patients with higher levels of these genes had more aggressive cancer, characterized by deeper uterine invasion, increased spread, and shorter survival times. These genes were also linked to immune system changes, suggesting they might help cancer cells avoid immune attack. In lab experiments, reducing cyclin B1 and B2 activity slowed cancer cell growth and decreased their ability to move and invade. These findings indicate that cyclin B1 and B2 promote endometrial cancer growth and spread. Measuring their levels could help predict cancer aggressiveness, and future treatments targeting these genes may offer new strategies to fight the disease.