CDCA8基因表达与膀胱癌患者临床病理和预后的相关性

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摘要目的探讨膀胱癌患者CDCA8基因的表达情况和CDCA8基因与膀胱癌的临床病理相关性及预后相关性,预测CDCA8是如何推动膀胱癌发生、发展及其机制。方法从NCBI(National Center for Biotechnology Information)的GEO数据库中下载膀胱癌基因表达数据GSE13507,采用非配对t检验分析CDCA8在膀胱癌中的表达情况,χ²检验分析CDCA8表达与膀胱癌患者临床病理指标的相关性,Log-rank检验用于预后生存分析;利用基因富集分析(GSEA)方法,分析CDCA8高表达样本的富集基因及受CDCA8调控的相关基因。结果膀胱癌中CDCA8表达水平明显高于正常膀胱组(8.87±0.08 vs 7.47±0.07, P<0.0001);CDCA8的表达与膀胱癌患者的年龄(P=0.027)、性别(P=0.04)及膀胱癌的疾病进展(P=0.001)、T分期(P<0.0001)、N分期(P=0.013)、不同分级(P<0.0001)密切相关;CDCA8高表达组膀胱癌患者的肿瘤特异性生存期明显短于CDCA8低表达组(P<0.0001, HR=0.5177, 95% CI: 13.40~18.10),且CDCA8高表达组膀胱癌患者的总生存期亦短于CDCA8低表达组(P<0.0001, HR=0.09906, 95% CI: 5.971~16.38);CDCA8可能调控与精子形成、G₂M检查点、E₂F信号通路、未折叠蛋白反应、MYC信号通路、MTORC1信号通路、有丝分裂纺锤体形成、PI3K/AKT/mTOR通路、胆固醇平衡、糖酵解相关的基因集。结论 CDCA8在膀胱癌组织中显著高表达,且与膀胱癌的恶性程度和发生进展相关,高表达CDCA8的膀胱癌患者临床预后更差,可能作为潜在的判断膀胱癌患者疾病进展的标志物和治疗膀胱癌的靶标。

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	毕娅琼
	陈松
	蒋佳志
	石宏杰
	李胜

关键词 ：膀胱癌, CDCA8, 临床意义

Abstract：Objective To investigate the expression of CDCA8 in bladder cancer (BC), to clarify the relationships between CDCA8 expressions and clinicopathological characteristics of BC and the prognostic value of CDCA8 in BC, and to evaluate the mechanism of CDCA8 in BC.Methods The bladder cancer sample expression profiles including CDCA8 expression data and its clinical information were downloaded from GEO datasets. The expression of CDCA8 in bladder cancer was analyzed by non-paired t test. The correlations between CDCA8 gene expression and the clinicopathologic features were analyzed by Chi-square test. Overall survival and specific survival were analyzed using Log-rank method. GSEA(gene set enrichment analysis)was conducted to explore the associated gene sets regulated by CDCA8.Results The expression of CDCA8 was up-regulated in BC (8.870±0.08281 vs 7.472±0.07035, P<0.0001). CDCA8 expression was significantly associated with age(P=0.027), gender(P=0.04), progression(P=0.001),T stage(P<0.0001), N stage(P=0.013)and grade(P<0.0001). Higher expressions of CDCA8 predicted both poor specific survival in BC(P<0.0001, HR= 0.5177, 95% CI: 13.40-18.10) and poor overall survival in BC(P<0.0001, HR=0.09906, 95% CI: 5.971-16.38). The Results of GSEA indicated that CDCA8 regulated gene sets associated with spermatogenesis, G₂M checkpoint, E₂F targets, Myc targets, mTORC1 signaling, mitotic spindle angiogenesis, PI3K/AKT/mTOR signaling, cholesterol homeostasis and glycolysis.Conclusions CDCA8 is highly expressed in BC, correlated with worse clinicopathological features and acts as a prognostic marker and target in the diagnosis and treatment of patients with BC.

Key words： bladder cancer CDCA8 clinical significance

收稿日期: 2017-11-20

ZTFLH:

R737.14

基金资助:中央高校基本科研业务费专项资金资助(2042018kf0077); 武汉大学珞珈青年学者科研基金(351人才计划)

通讯作者: 李胜,E-mail:lisheng-znyy@whu.edu.cn

作者简介: 毕娅琼,本科学历。

引用本文:

毕娅琼, 陈松, 蒋佳志, 石宏杰, 李胜. CDCA8基因表达与膀胱癌患者临床病理和预后的相关性[J]. 武警医学, 2018, 29(8): 750-754. BI Yaqiong, CHEN Song, JIANG Jiazhi, SHI Hongjie, LI Sheng. Expression of CDCA8 in bladder cancer and its clinical significance. Med. J. Chin. Peop. Armed Poli. Forc., 2018, 29(8): 750-754.

链接本文:

http://journal08.magtechjournal.com/Jwk_wjyx/CN/ 或 http://journal08.magtechjournal.com/Jwk_wjyx/CN/Y2018/V29/I8/750

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