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Bradeion(SEPT4)作为膀胱癌的尿生物标志物:基因表达的实时聚合酶链反应研究。

Bradeion (SEPT4) as a urinary marker of transitional cell bladder cancer: a real-time polymerase chain reaction study of gene expression.

机构信息

Department of Urology, Catholic University of the Sacred Heart, Policlinico Agostino Gemelli, Rome, Italy.

出版信息

J Urol. 2012 Jun;187(6):2223-7. doi: 10.1016/j.juro.2012.01.031. Epub 2012 Apr 13.

Abstract

PURPOSE

We evaluated whether Bradeion/SEPT4 gene expression could be used as a potential urinary marker to diagnose bladder transitional cell carcinoma.

MATERIALS AND METHODS

From 2005 to 2007 we collected urine samples from 58 individuals, 17 healthy controls and 41 patients in whom bladder tumors were previously diagnosed by cystoscopy. Urine was collected from all patients before transurethral resection of bladder tumor. We performed real-time reverse transcriptase-polymerase chain reaction to evaluate Bradeion/SEPT4 transcript levels using urine sample mRNA. Statistical analysis was done with the Mann-Whitney test and ROC curves.

RESULTS

Pathological examination of bladder tumor specimens revealed transitional cell bladder cancer. According to the 2002 TNM classification stage was Ta in 11 patients, T1 in 18 and T2/T3 in 12. All patients had G2 or G3 tumors according to the 1973 WHO grade classification. Relative quantification analysis of Bradeion transcript showed significantly increased levels compared to controls, namely 21.85 times higher in Ta stage tumors, 7.21 times higher in T1 tumors and 4.36 times higher in grade T2/T3 tumors. We compared each tumor stage group with the control group using the Mann-Whitney test to verify the statistical significance of observed differences. The ROC curve built on the change in threshold cycle revealed that with this method we attained 92.68% sensitivity and 64.71% specificity (AUC 0.798, p=0.0001).

CONCLUSIONS

Bradeion/SEPT4 transcript levels are significantly increased in patients with transitional cell bladder cancer compared to healthy controls. Our preliminary study supports the possible usefulness of Bradeion as a urinary marker of urothelial disease.

摘要

目的

我们评估 Bradeion/SEPT4 基因表达能否作为潜在的尿标志物用于诊断膀胱移行细胞癌。

材料与方法

我们于 2005 年至 2007 年收集了 58 例个体的尿液样本,其中 17 例为健康对照者,41 例患者曾经膀胱镜诊断为膀胱肿瘤。所有患者在经尿道膀胱肿瘤切除术之前采集尿液。我们使用尿液样本 mRNA 进行实时逆转录聚合酶链反应,评估 Bradeion/SEPT4 转录物水平。使用 Mann-Whitney 检验和 ROC 曲线进行统计分析。

结果

膀胱肿瘤标本的病理检查显示为移行细胞膀胱癌。根据 2002 年 TNM 分期,Ta 期 11 例,T1 期 18 例,T2/T3 期 12 例。根据 1973 年 WHO 分级分类,所有患者均为 G2 或 G3 肿瘤。与对照组相比,Bradeion 转录本的相对定量分析显示出明显升高的水平,即在 Ta 期肿瘤中升高 21.85 倍,在 T1 期肿瘤中升高 7.21 倍,在 G2/T3 期肿瘤中升高 4.36 倍。我们使用 Mann-Whitney 检验比较了每个肿瘤分期组与对照组,以验证观察到的差异的统计学意义。基于阈值循环变化构建的 ROC 曲线表明,使用该方法,我们获得了 92.68%的灵敏度和 64.71%的特异性(AUC 0.798,p=0.0001)。

结论

与健康对照者相比,Bradeion/SEPT4 转录物水平在患有移行细胞膀胱癌的患者中显著升高。我们的初步研究支持 Bradeion 作为尿路上皮疾病的潜在标志物的可能有用性。

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