CDCA8 expression and its clinical relevance in patients with bladder cancer.
CDCA8 expression and its clinical relevance in patients with bladder cancer.
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CDCA8表达及其在膀胱癌患者中的临床相关性。
DOI：
10.1097/md.0000000000011899
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发表时间：
2018-08
期刊：
影响因子：
1.6
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Bi Y;Chen S;Jiang J;Yao J;Wang G;Zhou Q;Li S
细胞分裂周期相关蛋白8（CDCA 8）在多种恶性肿瘤中存在过表达，并与肿瘤生长密切相关。然而，CDCA 8表达与膀胱癌临床病理因素及预后的关系尚不清楚。本研究的目的是确定CDCA 8在BC患者中的表达及其临床意义。采用GEO数据集获得BC样本中CDCA 8表达数据及其临床信息。采用实时荧光定量PCR（Real-time PCR，RT-PCR）检测CDCA 8在BC及癌旁正常组织中的表达。采用非配对t检验对两组间的差异进行统计学分析。采用考克斯单变量和多变量分析方法对BC患者的总生存期（OS）和癌症特异性生存期（CSS）进行分析。分析了可能介导BC中CDCA 8活性的生物学过程或信号通路。CDCA 8水平在BC中显著升高（8.870 ± 0.08281对7.472 ± 0.07035，P <0.0001）。 CDCA 8表达与肿瘤进展（P =.001）、T分期（P <.0001）、N分期（P =.013）和分级（P <.0001）显著相关。 CDCA 8的高表达预示着BC患者的癌症特异性生存率（P <0.0001，HR = 0.2752，95% CI：0.1364-0.5554）和总生存率（P <0.0001，HR = 0.4270，95% CI：0.2630-0.6930）较差。 考克斯单因素和多因素分析显示，膀胱灌注治疗、N分期和进展是膀胱癌患者总生存期的独立影响因素，CDCA 8表达、肿瘤分级和进展是膀胱癌患者肿瘤特异性生存期的独立影响因素。GSEA结果显示，CDCA 8调控的基因集与精子发生、G2 M检查点、E2 F靶点、Myc靶点、mTORC 1信号通路、有丝分裂纺锤体血管生成、PI 3 K/AKT/mTOR信号通路、胆固醇稳态和糖酵解相关。最后，RT-PCR结果证实，CDCA 8表达上调BC（P = 0.0039）。 CDCA 8在BC中过表达，其高水平与BC患者的不良临床病理特征相关。因此，CDCA 8可能作为一种新的预后标志物和治疗靶点，在诊断和治疗的BC患者。
Cell division cycle associated 8 (CDCA8) overexpression is detected in various malignant tumors and closely associated with tumor growth. However, the correlations of CDCA8 expression with clinicopathological factors and prognosis of bladder cancer (BC) remain unclear. The purpose of this study was to identify the expression of CDCA8 and its clinical relevance in BC patients. GEO datasets were employed to obtain CDCA8 expression data and its clinical information in BC samples. Real-time PCR (RT-PCR) was performed to detect the expression of CDCA8 in BC and the adjacent normal tissues. Nonpaired t test was used to statistically analyze the difference between the 2 groups. Cox univariable and multivariable analyses of overall survival (OS) and cancer specific survival (CSS) among BC patients were performed. Biological processes or signaling pathways that might mediate the activity of CDCA8 in BC were analyzed. CDCA8 levels were significantly higher in BC (8.870 ± 0.08281 vs 7.472 ± 0.07035, P < .0001). CDCA8 expression was significantly associated with tumor progression (P = .001), T stage (P < .0001), N stage (P = .013), and grade (P < .0001). Higher expression of CDCA8 predicted poor cancer-specific survival (P < .0001, HR = 0.2752, 95% CI:0.1364-0.5554) and overall survival (P < .0001, HR = 0.4270, 95% CI: 0.2630–0.6930) in patients with BC. Cox univariable and multivariable analyses showed that intravesical therapy, N stage and progression were the independent influence factors of overall survival among bladder cancer patients, CDCA8 expression, tumor grade and progression were the independent influence factors of cancer specific survival among bladder cancer patients. 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. Finally, RT-PCR results confirmed that CDCA8 expression was upregulated in BC (P = .0039). CDCA8 is overexpressed in BC and its high levels are correlated with poor clinicopathological features of BC patients. Therefore, CDCA8 may act as a novel prognostic marker and therapeutical target in the diagnosis and treatment of patients with BC.