Li Zhilong, Su Min, Li Qin, Zheng Xuelian, Song Yaping, Wang Yanyun, Zhou Bin, Zhang Lin
Laboratory of Molecular Translational Medicine, Center for Translational Medicine; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education; Children's Medicine Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
BMC Cancer. 2025 Apr 16;25(1):714. doi: 10.1186/s12885-025-14132-w.
Cyclin-dependent kinase 8 (CDK8) has been implicated in various tumors, with its role differing across tumor types. However, the association between CDK8 polymorphisms and bladder cancer (BC) remains unclear. This study investigated the association between CDK8 polymorphisms and BC susceptibility and prognosis.
This case-control study included 271 patients with BC and 381 healthy controls. Two-tag single-nucleotide polymorphisms in the CDK8 gene (rs17083838 and rs7992670) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed using SNPstats and SPSS software to assess genetic associations.
The AG/AA genotypes of rs17083838 were associated with a significantly reduced risk of BC under the dominant model (P < 0.001, odds ratio [95% confidence interval] = 0.50 [0.33-0.76]). Stratified analysis revealed that the AG genotype of rs17083838 increased the risk of postoperative recurrence in patients with stage IV BC (P = 0.007). For rs7992670, females with the AG/AA genotype exhibited a 2.07-fold higher risk of BC than males, whereas smokers with the same genotype showed a 2.13-fold higher risk than non-smokers. The GG genotype of rs7992670 was associated with better overall survival in patients with stage III BC (P = 0.023). Among patients with recurrent muscle-invasive BC, those with the GG/AA genotype showed significantly improved survival compared with those carrying the AG genotype (P = 0.023).
CDK8 polymorphisms influence BC susceptibility and prognosis, with rs17083838 showing a protective effect and rs7992670 being associated with increased risk and survival outcomes in specific subgroups.
This study highlights the potential of CDK8 polymorphisms as biomarkers for BC susceptibility and prognosis, emphasizing the need for further research.
细胞周期蛋白依赖性激酶8(CDK8)与多种肿瘤有关,其在不同肿瘤类型中的作用有所不同。然而,CDK8基因多态性与膀胱癌(BC)之间的关联仍不清楚。本研究调查了CDK8基因多态性与BC易感性及预后之间的关联。
本病例对照研究纳入了271例BC患者和381例健康对照。使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对CDK8基因中的两个标签单核苷酸多态性(rs17083838和rs7992670)进行基因分型。使用SNPstats和SPSS软件进行统计分析以评估基因关联。
在显性模型下,rs17083838的AG/AA基因型与BC风险显著降低相关(P < 0.001,比值比[95%置信区间]= 0.50 [0.33 - 0.76])。分层分析显示,rs17083838的AG基因型增加了IV期BC患者术后复发的风险(P = 0.007)。对于rs7992670,AG/AA基因型的女性患BC的风险比男性高2.07倍,而相同基因型的吸烟者患BC的风险比非吸烟者高2.13倍。rs7992670的GG基因型与III期BC患者更好的总生存期相关(P = 0.023)。在复发性肌肉浸润性BC患者中,GG/AA基因型的患者与携带AG基因型的患者相比,生存期显著改善(P = 0.023)。
CDK8基因多态性影响BC易感性和预后,rs17083838显示出保护作用,rs7992670与特定亚组中风险增加和生存结果相关。
本研究强调了CDK8基因多态性作为BC易感性和预后生物标志物的潜力,强调了进一步研究的必要性。