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首页> 外文期刊>Journal of the National Cancer Institute >Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection.
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Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection.

机译:定量分析尿沉渣中的Aurora激酶A基因拷贝数和检测膀胱癌。

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摘要

BACKGROUND: Chromosome missegregation and the resulting aneuploidy is a common change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key regulator of mitosis, is frequently amplified and/or overexpressed in cancer cells, and the level of AURKA amplification is associated with the level of aneuploidy. We examined whether AURKA gene amplification is a biomarker for the detection of bladder cancer. METHODS: The effect of ectopic expression of Aurora kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number was measured in vitro by immunofluorescence and fluorescence in situ hybridization (FISH), respectively. The FISH test was also used to examine AURKA gene copy number in exfoliated cells in voided urine samples from 23 patients with bladder cancer and 7 healthy control subjects (training set), generating a model for bladder cancer detection that was subsequently validated in an independent set of voided urine samples from 100 bladder cancer patients and 148 control subjects (92 healthy individuals and 56 patients with benign urologic disorders). An AURKA gene score (the proportion of cells with three or more AURKA signals) was used to produce receiver operating characteristic (ROC) curves and to calculate the specificity and sensitivity of the AURKA FISH test. Differences between mean AURKA scores in different pathogenetic groups of bladder cancer stratified according to histological grade and stage were tested by unpaired Mann-Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided. RESULTS: Forced overexpression of AURKA in urothelial cells induced amplification of centrosomes, chromosome missegregation, and aneuploidy, and natural overexpression was detectable in in situ lesions from patients with bladder cancer. The FISH test for the AURKA gene copy number performed on the validation set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3%to 98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC curve of 0.939 (95% CI = 0.906 to 0.971; P < .001). CONCLUSION: Overexpression of AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is a promising biomarker for detection of bladder cancer.
机译:背景:染色体错聚和由此产生的非整倍性是瘤形成中的常见变化。编码有丝分裂的关键调节因子的Aurora激酶A(AURKA)基因在癌细胞中经常被扩增和/或过表达,并且AURKA扩增的水平与非整倍性水平相关。我们检查了AURKA基因扩增是否是检测膀胱癌的生物标记。方法:通过免疫荧光和荧光原位杂交技术在体外测量猿病毒40永生化尿路上皮细胞(SV-HUC)中腺病毒载体异位表达Aurora激酶A(AURKA)对中心体增殖和染色体拷贝数的影响(鱼)。 FISH测试还用于检查23名膀胱癌患者和7名健康对照受试者(训练组)的排尿样品中脱落细胞中脱落细胞中AURKA基因的拷贝数,从而建立了膀胱癌检测模型,随后在独立组中对其进行了验证100位膀胱癌患者和148位对照受试者(92位健康个体和56位患有良性泌尿系统疾病的患者)的尿液样本进行了分析。使用AURKA基因评分(具有三个或更多AURKA信号的细胞比例)来生成接收器工作特征(ROC)曲线,并计算AURKA FISH测试的特异性和敏感性。通过不配对Mann-Whitney t检验或单向Wilcoxon检验,对根据组织学等级和阶段分层的膀胱癌不同致病组的平均AURKA得分之间的差异进行了检验。所有统计检验都是双面的。结果:尿道上皮细胞中强迫性AURKA过表达引起中心体扩增,染色体错集和非整倍性,并且在膀胱癌患者的原位病变中可检测到自然过表达。在验证集上进行的AURKA基因拷贝数的FISH测试得出特异性为96.6%(95%置信区间[CI] = 92.3%至98.5%),敏感性为87%(95%CI = 79.0%至92.2%) )和ROC曲线下的面积为0.939(95%CI = 0.906至0.971; P <.001)。结论:AURKA的过度表达可引起尿路上皮细胞非整倍性,AURKA基因拷贝数是检测膀胱癌的有前途的生物标志物。

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