Prognostic Evaluation and Functional Characterization of Cyclin K Expression in Endometrial Cancer: Immunohistochemical and In Silico Analysis

TL;DR

This study finds that higher cyclin K levels in endometrial cancer tissues are linked to worse survival, especially in aggressive cancer subtypes.

Contribution

The study provides new evidence on cyclin K's role in endometrial cancer prognosis and its functional involvement in RNA metabolism and transcription.

Findings

CCNK expression is elevated in endometrial cancer tissues compared to normal samples.

High CCNK levels correlate with worse overall survival in non-endometrioid subtypes.

CCNK is functionally linked to RNA metabolism and transcriptional regulation.

Abstract

This study examines the expression of cyclin K (CCNK) in endometrial cancer by comparing immunohistochemical analysis (IHC) with gene expression data from The Cancer Genome Atlas (TCGA) across endometrioid and non-endometrioid types and evaluates its correlation with patient survival outcomes. Our findings indicate that CCNK expression is elevated in endometrial cancer tissues compared to normal endometrial samples. Higher protein and mRNA expression levels were associated with worse overall survival (OS). A functional enrichment analysis of genes linked to CCNK suggests its involvement in transcriptional regulation and RNA metabolism. These results contribute to understanding the potential role of CCNK in tumor biology and its prognostic significance 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.

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