Mechanistic Insights Into the Tumor-Driving and Diagnostic Roles of KCTD Family Genes in Ovarian Cancer: An Integrated In Silico and In Vitro Analysis.

BACKGROUND: Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, characterized by late-stage diagnosis and high recurrence rates. Despite advances in treatment, the overall survival rate for OC patients remains low due to the lack of reliable biomarkers for early detection and prognosis. Thus, there is an urgent need for novel diagnostic and prognostic biomarkers to improve patient outcomes. In this study, we explored the potential role of the KCTD (Potassium Channel Tetramerization Domain-containing) family genes in OC. METHODS: This study utilized comprehensive in silico and in vitro experiments. RESULTS: Firstly, we analyzed the expression patterns of KCTD genes across 12 OC cell lines and 6 normal control cell lines using RT-qPCR, identifying significant upregulation of KCTD5, KCTD9, KCTD12, and KCTD16, while KCTD2, KCTD10, KCTD15, and KCTD21 were downregulated. ROC analysis revealed high diagnostic accuracy for KCTD2, KCTD5, KCTD9, and KCTD12. Further stage-specific analysis indicated that KCTD2, KCTD5, KCTD15, and KCTD21 are associated with OC progression. Functional assays in SKOV3 and A2780 cells demonstrated that overexpression of KCTD2 and KCTD10 significantly inhibited cell proliferation, migration, and colony formation, suggesting their tumor-suppressive roles. Immune and drug sensitivity analyses revealed that KCTD genes may influence immune evasion and chemoresistance in OC. Additionally, miRNA analysis identified potential regulatory mechanisms of KCTD expression. CONCLUSION: Collectively, our findings indicate that KCTD family members serve as promising biomarkers, offering new insights into therapeutic strategies for OC management. Further validation in clinical settings is essential to establish their potential as therapeutic targets.