Zhang Ling, Cheng Chong, Tang Bin
Centre for Reproductive Medicine, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, China.
Department of Nuclear Medicine, Changde Hospital, Xiangya School of Medicine, Central South University (The first people's hospital of Changde city), Changde, China.
Cancer Med. 2025 Aug;14(16):e71147. doi: 10.1002/cam4.71147.
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.
This study utilized comprehensive in silico and in vitro experiments.
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.
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.
卵巢癌(OC)仍然是最致命的妇科恶性肿瘤之一,其特征是诊断较晚且复发率高。尽管治疗方面取得了进展,但由于缺乏用于早期检测和预后的可靠生物标志物,OC患者的总体生存率仍然很低。因此,迫切需要新的诊断和预后生物标志物来改善患者的治疗效果。在本研究中,我们探讨了含钾通道四聚化结构域(KCTD)家族基因在OC中的潜在作用。
本研究利用了全面的计算机模拟和体外实验。
首先,我们使用RT-qPCR分析了12种OC细胞系和6种正常对照细胞系中KCTD基因的表达模式,发现KCTD5、KCTD9、KCTD12和KCTD16显著上调,而KCTD2、KCTD10、KCTD15和KCTD21下调。ROC分析显示KCTD2、KCTD5、KCTD9和KCTD12具有较高的诊断准确性。进一步的阶段特异性分析表明,KCTD2、KCTD5、KCTD15和KCTD21与OC进展相关。在SKOV3和A2780细胞中的功能测定表明,KCTD2和KCTD10的过表达显著抑制细胞增殖、迁移和集落形成,表明它们具有肿瘤抑制作用。免疫和药物敏感性分析表明,KCTD基因可能影响OC中的免疫逃逸和化疗耐药性。此外,miRNA分析确定了KCTD表达的潜在调控机制。
总体而言,我们的研究结果表明,KCTD家族成员有望成为生物标志物,为OC治疗策略提供新的见解。在临床环境中进行进一步验证对于确定它们作为治疗靶点的潜力至关重要。