国际肿瘤学杂志

国际肿瘤学杂志 ›› 2018, Vol. 45 ›› Issue (1): 22-.doi: 10.3760/cma.j.issn.1673-422X.2018.01.005

• 论著 • 上一篇    下一篇

TOP2A基因表达对膀胱癌的预后价值分析

袁佳仪，何恒晶，毕娅琼，郭梓鑫，肖宇，李胜   

  1. 430071 武汉大学中南医院生物样本库（袁佳仪、何恒晶、毕娅琼、郭梓鑫、肖宇、李胜），泌尿外科（肖宇、 李胜），精准医学实验室（肖宇、李胜）；武汉市泌尿男生殖系肿瘤临床研究中心（肖宇、李胜）
  • 出版日期:2018-01-08 发布日期:2018-02-12
  • 通讯作者: 李胜 E-mail:lishengznyy@whu.edu.cn
  • 基金资助:
    国家自然科学基金（81772730）；珞珈青年学者科研基金（武汉大学“351人才计划”）

Prognostic value analysis of TOP2A gene expression for bladder cancer

Yuan Jiayi, He Hengjing, Bi Yaqiong, Guo Zixin, Xiao Yu, Li Sheng   

  1. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
  • Online:2018-01-08 Published:2018-02-12
  • Contact: Li Sheng E-mail:lishengznyy@whu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (81772730); Luojia Young Scholars Research Fund (the 351 Talent Project of Wuhan University)

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860

被引次数

7

摘要： 目的探讨DNA拓扑异构酶Ⅱα（TOP2A）基因表达与膀胱癌患者临床病理特征的关系及其对预后评价的意义。方法收集膀胱癌基因表达谱数据集GSE13507（n=165）和GSE31189（n=52），对膀胱癌患者样本表达谱资料及其对应的临床信息进行病理指标的回顾性分析和生存期分析；利用基因集富集分析（GSEA）方法预测受TOP2A调控的相关通路。结果TOP2A基因在膀胱癌组织中的表达水平明显高于其在正常膀胱组织中的表达（5.823±1.079∶4.820±1.129），差异有统计学意义（t=4.336，P＜0.001）。TOP2A基因在膀胱癌中的表达与患者年龄（χ2=5.926，P=0.015）、性别（χ2=6.046，P=0.014）、T分期（χ2=19.484，P＜0.001）、N分期（χ2=9.178，P=0.002）、M分期（χ2=21.142，P＜0.001）、疾病分级（χ2=47.005，P＜0.001）、病情进展（χ2=11.735，P=0.001）有关，而与肿瘤是否复发（χ2=0.808，P=0.369）无明显相关性。生存分析结果显示，TOP2A基因高表达组患者第100个月时的肿瘤特异性生存率明显低于TOP2A低表达组患者（66.59%∶87.95%），差异有统计学意义（χ2=15.820，P＜0.001）；TOP2A高表达组和低表达组患者的中位总生存期分别为51.77个月和134.97个月，差异有统计学意义（χ2=11.280，P=0.008）。GSEA结果提示TOP2A可能调节了MYCV1信号通路（P=0.035，FDR=0.132）、MYCV2信号通路（P=0.012，FDR=0.058）、E2F信号通路（P＜0.001，FDR=0.006）和G2M检查点（P=0.006，FDR=0.044）相关的基因集。结论TOP2A基因表达与膀胱癌患者的临床病理特征密切相关，TOP2A可作为潜在的判断膀胱癌患者预后的标志物。

关键词: DNA拓扑异构酶类, Ⅱ型； 膀胱肿瘤； 基因表达； 预后

Abstract: ObjectiveTo investigate the relationship between DNA topoisomerase Ⅱα (TOP2A) gene expression and clinicopathological characteristics and its significance of prognostic evaluation for patients with bladder cancer. MethodsBladder cancer gene expression profile GSE13507 (n=165) and GSE31189 (n=52) were obtained. The expression profile and clinical information of patients with bladder cancer were retrospectively analyzed, and the survival analysis was made. Gene set enrichment analysis (GSEA) was conducted to explore the related pathways which were regulated by TOP2A. ResultsCompared with normal bladder tissues, TOP2A was upregulated in bladder cancer tissues (5.823±1.079 vs. 4.820±1.129), with a statistically significant difference (t=4.336, P＜0.001). The TOP2A gene expression in patients with bladder cancer was correlated with the age of patients (χ2=5.926, P=0.015), sex (χ2=6.046, P=0.014), T staging (χ2=19.484, P＜0.001), N staging (χ2=9.178, P=0.002), M staging (χ2=21.142, P＜0.001), tumor grade (χ2=47.005, P＜0.001), and progression (χ2=11.735, P=0.001), but it was not correlated with recurrence (χ2=0.808, P=0.369). Survival analysis showed that the specific survival rate in the 100 months of TOP2A gene high expression group and low expression group had a statistically significant difference (66.59% vs. 87.95%, χ2=15.820, P＜0.001). The median overall survival time of TOP2A gene high expression group and low expression group were 51.77 months and 134.97 months respectively, with a statistically significant difference (χ2=11.280, P=0.008). The results of GSEA indicated that TOP2A could regulate gene sets related with several pathways like MYCV1 signaling (P=0.035, FDR=0.132), MYCV2 signaling (P=0.012, FDR=0.058), E2F signaling (P<0.001, FDR=0.006) and G2M checkpoint (P=0.006, FDR=0.044). ConclusionThe TOP2A gene expression is closely related with clinicopathological characteristics of patients with bladder cancer. TOP2A may function as a potential marker of prognosis for patients with bladder cancer.

Key words: DNA topoisomerases, type Ⅱ, Urinary bladder neoplasms, Gene expression, Prognosis