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

BACKGROUND

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.

METHODS

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 in vitro.

RESULTS

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 in vitro.

CONCLUSIONS

CCNB1 and CCNB2 may serve as potential prognostic markers and therapeutic targets for the management of EC.