Prognostic Evaluation and Functional Characterization of Cyclin K Expression in Endometrial Cancer:...

Background/Objectives: Endometrial cancer (EC) is a heterogeneous gynecological malignancy characterized by varied clinical outcomes and complex molecular mechanisms. The dysregulation of cyclin K (CCNK), a key regulator of transcription and cell cycle progression, has been implicated in cancer development. This study aimed to investigate CCNK expression at the protein level in EC tissues and at the mRNA level using in silico analysis. Additionally, the prognostic significance of CCNK expression in EC was assessed. Methods: CCNK expression was evaluated using immunohistochemical analysis and mRNA expression profiling in EC tissues, adjacent non-tumorous tissues, and histologically normal endometrial tissues. Immunohistochemical staining was performed on tissue macroarrays, and protein expression was quantified using the Immunoreactivity Score (IRS). mRNA expression analysis was conducted in silico using TCGA data via UCSC Xena and UALCAN web tool. Pathway enrichment was analyzed using Reactome and DAVID tool, while PPI networks were constructed with STRING and Cytoscape. Statistical analyses, including Mann-Whitney U test, Fisher's exact test, Chi-square test, Kaplan-Meier survival analysis, and Cox regression, were performed using GraphPad Prism. Results: Immunohistochemical analysis revealed significantly elevated CCNK protein expression in tumor tissues, particularly in advanced-stage cases, correlating with adverse pathological features such as higher tumor stage and FIGO grade. High CCNK protein expression was significantly associated with poorer OS in the overall EC cohort and non-endometrioid subtypes, whereas no significant association was observed in endometrioid subtypes. mRNA expression analysis demonstrated significantly higher CCNK levels in non-endometrioid tumors compared to adjacent non-tumorous tissues, but no significant correlation with OS was observed. Functional enrichment analysis highlighted the involvement of CCNK-associated genes in RNA metabolism and transcriptional regulation. Conclusions: These findings emphasize the prognostic value of CCNK expression in EC, particularly in aggressive subtypes. The results suggest that CCNK may serve as a potential therapeutic target, warranting further investigation into its role in EC progression and treatment strategies.