摘要
通过生物信息学分析结合细胞与动物实验,探讨了驱动蛋白家族成员15(KIF15)在前列腺癌中的潜在临床价值,尤其是其作为预后生物标志物及治疗靶点的作用.首先从TCGA数据集中提取KIF15的表达数据及相关临床信息,采用无监督聚类分析建立分子亚型,并对不同亚型的预后进行比较.通过最小绝对收缩和选择算子(LASSO)回归分析,构建了基于KIF15的风险模型,并利用前列腺癌数据库进行验证.此外,采用列线图对患者生存期进行了预测.细胞实验结果表明,KIF15的敲低显著抑制前列腺癌细胞的增殖与迁移能力,相关的克隆形成、免疫印迹和Transwell实验均支持这一结论.机制分析显示,KIF15通过调控下游因子CDCA8,影响肿瘤细胞的M期活性.动物实验进一步验证了靶向敲低KIF15可以有效抑制肿瘤的进展.综上所述,KIF15不仅是前列腺癌预后的独立风险因素,还为该疾病的靶向治疗提供了新的潜在靶点.
Through bioinformatics analysis combined with cellular and animal experiments,the potential clinical value of kinesin family member 15(KIF15)in prostate cancer was explored,particularly its role as a prognostic biomarker and therapeutic target.First,the expression data of KIF15 and related clinical information were extracted from the TCGA dataset.Unsupervised clustering analysis was employed to establish molecular subtypes,and the prognostic outcomes of different subtypes were compared.A risk model based on KIF15 was constructed through LASSO regression analysis and validated using a prostate cancer database.Additionally,a nomogram was employed to predict patient survival.Cellular experiments demonstrated that the knockdown of KIF15 significantly inhibited the proliferation and migration capabilities of prostate cancer cells,with findings from colony formation,Western blot,and Transwell assays supporting this result.Mechanistic analysis revealed that KIF15 regulates the downstream factor CDCA8,affecting the mitotic activity of tumor cells.In vivo experiments further confirmed that targeting KIF15 effectively suppressed tumor progression.In conclusion,KIF15 not only serves as an independent prognostic risk factor for prostate cancer but also provides a novel potential target for targeted therapy in this disease.
作者
李晓晴
宋玥
王贵鑫
范中强
田晶
Li Xiaoqing;Song Yue;Wang Guixin;Fan Zhongqiang;Tian Jing(PhaseⅠClinical Trial Department,National Clinical Research Center for Cancer,Tianjin Medical University Cancer Institute&Hospital,Tianjin 300060,China;Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China;Key Laboratory of Cancer Prevention and Therapy,Tianjin 300060,China;The First Department of Breast Cancer,National Clinical Research Center for Cancer,Tianjin Medical University Cancer Institute&Hospital,Tianjin 30o060,China;Department of Urology,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Urology,The Second Hospital of Tianjin Medical University,Tianjin 300211,China)
出处
《南开大学学报(自然科学版)》
北大核心
2025年第5期34-40,共7页
Journal of Nankai University(Natural Sience)
基金
天津医科大学肿瘤医院院级课题国自然基金培育项目(220107)
天津市重大项目(21ZXJBSY00090)
天津市卫生健康科技项目(TJWJ2024QN015)
天津市医学重点学科建设资助(TJYXZDXK-3-003A)。
