Background: Uterine corpus endometrial carcinoma (UCEC) is the fourth most common cancer among women worldwide. The 5 year survival rate for patients with advanced UCEC is only 17%. Lysine-specific demethylase 4B (KDM4B), a histone demethylase, is overexpressed or dysregulated in various cancers and is associated with tumor progression and poor prognosis. We performed bioinformatics analysis and in vitro assays to assess the role of KDM4B in UCEC. Additionally, the role of KDM4B in the tumor immune microenvironment was explored.
Methods: The mRNA and protein levels of KDM4B in UCEC were evaluated using The Cancer Genome Atlas (TCGA), The Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO) databases. Immunohistochemistry and western blotting were performed to verify the protein expression level of KDM4B in two batches of clinical samples. Kaplan-Meier survival, univariate, and multivariate analyses were performed to assess the correlation between KDM4B expression and the prognosis of patients with UCEC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the function and mechanism of KDM4B, and four immune-related databases (TIMER, CIBERSORT, TISIDB, and EPIC) were used to explore their relevance in a tumor immune microenvironment.
Results: First, KDM4B was significantly overexpressed in UCEC tissues at the mRNA and protein levels. Immunohistochemistry and western blotting confirmed the abnormal overexpression of KDM4B. Additionally, upregulation of KDM4B was associated with different clinicopathological prognostic factors. Second, the overexpression of KDM4B was also associated with shorter overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses confirmed that KDM4B was an independent prognostic factor for poor survival. Then, GO and KEGG analysis revealed that KDM4B is enriched in biological processes and cellular signaling pathways closely related to the immune response. Finally, KDM4B expression was closely associated with immune cell infiltration and expression of immune checkpoint molecules, indicating that it may be a new immune-related potential oncogene in UCEC.
Conclusions: KDM4B may be a new potential oncogene that is clinically significant in patients with UCEC. KDM4B may not only be used to assess the clinical prognosis of patients with UCEC but may also be a target for immunotherapy or targeted gene therapy.