DD3PCA3-based molecular urine analysis for the diagnosis of prostate cancer
DD3PCA3-based molecular urine analysis for the diagnosis of prostate cancer
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DOI：
10.1016/s0302-2838(03)00201-x
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发表时间：
2003-07-01
期刊：
影响因子：
23.4
通讯作者：
Schalken, JA
中科院分区：
文献类型：
--
作者：
Hessels, D;Gunnewiek, JMTK;Schalken, JA
背景：DD 3（PCA 3）是目前已知的前列腺癌特异性基因。为评价DD 3（PCA 3）的临床应用价值，建立了DD 3（PCA 3）的时间分辨荧光定量RT-PCR分析方法。此外，DD 3（PCA 3）转录定量测定前列腺按摩后获得的尿沉渣。结果：前列腺肿瘤显示DD 3（PCA 3）上调66倍（中位数158.4）。10（5）拷贝/μ g组织RNA）相比，良性前列腺组织（中位数2.4。10（5）拷贝/μ g组织RNA）。在研究的95%以上的前列腺癌标本中发现了这种上调。这些数据表明，具有小于10%的癌细胞的样本可以准确地与非癌组织区分开。因此，在正常细胞的背景下检测一小部分前列腺癌细胞似乎是可行的。因此，这种基于DD 3（PCA 3）的RT-PCR测定用于鉴定前列腺按摩后获得的尿沉淀中的前列腺癌。在108名血清PSA值>3 ng/ml的男性中，24名男性在活检时显示患有前列腺癌。在这24名男性中，16名显示DD 3（PCA 3）阳性，表明检测的灵敏度为67%。此外，阴性预测值为90%.Conclusion：DD 3（PCA 3）的定量RT-PCR检测描述，作为一种工具，分子尿液分析，有很大的希望。它在减少不必要的活检数量方面具有很大的潜力。使用DD 3（PCA 3）检测的多中心研究可为临床泌尿外科实践中的分子诊断实用性提供基础。(C)2003 Elsevier Science B. V.保留所有权利。
Background: DD3(PCA3) is the most prostate cancer-specific gene described to date. To assess the clinical utility of DD3(PCA3) a time-resolved fluorescence-based, quantitative RT-PCR analysis for DD3(PCA3) was developed.Methods: The diagnostic potential of DD3(PCA3) was determined by quantitative measurement of DD3(PCA3) transcripts in non-malignant and malignant prostate specimens. Moreover, DD3(PCA3) transcripts were determined quantitatively in urine sediments obtained after prostatic massage. A cohort of 108 men, admitted for prostate biopsies based on a PSA of >3 ng/ml, was studied.Results: Prostate tumors showed a 66-fold up-regulation of DD3(PCA3) (median 158.4 . 10(5) copies/mug tissue RNA) when compared to benign prostate tissue (median 2.4 . 10(5) copies/mug tissue RNA). This up-regulation was found in more than 95% of prostate cancer specimens studied. These data revealed that specimens with less than 10% of cancer cells could be accurately discriminated from non-cancer tissues. Hence, detection of a small fraction of prostate cancer cells in a background of normal cells seemed feasible. Therefore, this DD3(PCA3)-based RT-PCR assay was used for the identification of prostate cancer in urine sediments obtained after prostatic massage. From 108 men with a serum PSA value >3 ng/ml, 24 men were shown to have prostate cancer upon biopsy. Of these 24 men, 16 were shown to be positive for DD3(PCA3), indicating a sensitivity of the assay of 67%. Furthermore, a negative predictive value of 90% was calculated.Conclusion: The quantitative RT-PCR assay for DD3(PCA3) described, bears great promise as a tool for molecular urine analysis. It has great potential in reducing the number of unnecessary biopsies. A multi-center study using this DD3(PCA3) assay can provide the basis for the utility of molecular diagnostics in clinical urological practice. (C) 2003 Elsevier Science B.V. All rights reserved.