Wang Jie, Lai Xuejia, Sun Zhijun, Feng Sike, Li Bi, Zhao Hu
Department of Urology, Ningbo Ninth Hospital, No.68, Xiangbei Road, Ningbo, Zhejiang, 315000, PR China.
Department of General Surgery, 900 Hospital of the Joint Logistics Support Force, 156 Xierhuan Road, Fuzhou, Fujian, 350025, PR China.
BMC Urol. 2025 Apr 4;25(1):74. doi: 10.1186/s12894-025-01732-8.
Kinesin family member 14 (KIF14) is a significant multifunctional protein that has been linked to several malignancies. However, the varied expression profiles of KIF14 and its prognostic relevance in Clear cell renal cell carcinoma (ccRCC) have yet to be elucidated.
Patients with ccRCC were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. A comparison of KIF14 expression levels between ccRCC and normal tissues was conducted using the Wilcoxon rank sum test. Logistic regression analysis was subsequently employed to evaluate the relationship between KIF14 expression and clinicopathological features. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) term analysis, gene set enrichment analysis (GSEA) and single sample gene set enrichment analysis (ssGSEA), as well as CIBERSORT, were utilized to elucidate the enriched pathways and functions linked to KIF14 and to quantify the level of immune cell infiltration. Kaplan-Meier analysis was conducted to assess the correlation between KIF14 expression and survival. Additionally, KIF14 expression was downregulated in A498 ccRCC cells, and their proliferation, expansion capacity, cell cycle, and apoptosis were assessed through CCK-8 assays, colony formation assays, 7-AAD staining, and Annexin V/PI staining, respectively.
The findings of this study demonstrate that KIF14 mRNA levels are notably increased in ccRCC. Furthermore, a positive association was observed between KIF14 expression and cancer stage, nodal metastasis, and the infiltration of various immune cells in ccRCC. High levels of KIF14 were also found to be indicative of poor survival outcomes among ccRCC patients. Knockdown of KIF14 in A498 cells resulted in reduced proliferation, diminished colony formation capacity, cell cycle arrest, increased apoptosis, and downregulation of CyclinD1 and CDK4.
KIF14 down-regulates cell cycle proteins CyclinD1 and CDK4 to facilitate the proliferation of ccRCC cells, suggesting its potential as a therapeutic target and prognostic biomarker in ccRCC.
驱动蛋白家族成员14（KIF14）是一种重要的多功能蛋白，与多种恶性肿瘤相关。然而，KIF14在透明细胞肾细胞癌（ccRCC）中的不同表达谱及其预后相关性尚未阐明。
从癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和ArrayExpress数据库中获取ccRCC患者。使用Wilcoxon秩和检验比较ccRCC组织和正常组织之间的KIF14表达水平。随后采用逻辑回归分析评估KIF14表达与临床病理特征之间的关系。此外，利用基因本体（GO）和京都基因与基因组百科全书（KEGG）术语分析、基因集富集分析（GSEA）和单样本基因集富集分析（ssGSEA）以及CIBERSORT来阐明与KIF14相关的富集途径和功能，并量化免疫细胞浸润水平。采用Kaplan-Meier分析评估KIF14表达与生存之间的相关性。此外，在A498 ccRCC细胞中下调KIF14表达，并分别通过CCK-8测定、集落形成测定、7-AAD染色和Annexin V/PI染色评估其增殖、扩增能力、细胞周期和凋亡情况。
本研究结果表明，ccRCC中KIF14 mRNA水平显著升高。此外，观察到KIF14表达与ccRCC的癌症分期、淋巴结转移以及各种免疫细胞浸润之间呈正相关。高水平的KIF14还表明ccRCC患者的生存结果较差。敲低A498细胞中的KIF14导致增殖减少、集落形成能力降低、细胞周期停滞、凋亡增加以及细胞周期蛋白D1（CyclinD1）和细胞周期蛋白依赖性激酶4（CDK4）下调。
KIF14下调细胞周期蛋白CyclinD1和CDK4以促进ccRCC细胞增殖，提示其作为ccRCC治疗靶点和预后生物标志物的潜力。
