Prospective Multicentre Evaluation of PCA3 and TMPRSS2-ERG Gene Fusions as Diagnostic and Prognostic Urinary Biomarkers for Prostate Cancer
Prospective Multicentre Evaluation of PCA3 and TMPRSS2-ERG Gene Fusions as Diagnostic and Prognostic Urinary Biomarkers for Prostate Cancer
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DOI：
10.1016/j.eururo.2012.11.014
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发表时间：
2014-03-01
期刊：
影响因子：
23.4
通讯作者：
Schalken, Jack A.
中科院分区：
文献类型：
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作者：
Leyten, Gisele H. J. M.;Hessels, Daphne;Schalken, Jack A.
背景：前列腺癌抗原3(PCA3)和v-ETS红细胞增多症病毒E26癌基因同源基因(TMPRSS2-ERG)基因融合是一种有前景的前列腺癌(Pca)特异性生物标志物，可用于尿液检测。目的：评价前列腺癌PCA3和TMPRSS2-ERG基因融合(作为个体生物标志物和组合)对前列腺癌的诊断和预后价值。设计、背景和参与者：前瞻性收集来自6个中心的497名男性前列腺活检前的指检后首次取尿标本。我们评估了Progensa PCA3和TMPRSS2-ERG(定量核酸扩增检测TMPRSS2-ERG信使RNA[mRNA])对PCa、Gleason评分、临床肿瘤分期和PCa意义的预测价值(单独和作为标记小组)。这与血清前列腺特异性抗原和欧洲前列腺癌筛查随机研究(ERSPC)风险计算器进行了比较。在一个亚组(n=61)中，我们评估了生物标记物与前列腺切除术结果的相关性。结果测量和统计分析：使用了单变量和多变量Logistic回归分析以及接收器操作曲线。结果和局限性：443名男性的尿样中含有足够的RNA形式标记物分析。在443名男性中，有196人被诊断为前列腺癌。在多变量分析中，PCA3和TMPRSS2-ERG对ERSPC风险计算器参数有显著的额外预测价值(p<；0.001和。P=0.002)。曲线下面积(AUC)从0.799(ERSPC风险计算器)、0.833(ERSPC风险计算器+PCA3)、0.842(ERSPC风险计算器+PCA3+TMPRSS2ERG)增加到预测PCa。PCA3与TMPRSS2ERG联合应用时，敏感性由68%提高到76%。结论：TMPRSS2-ERG对PCA3和ERSPC风险计算器参数具有独立的附加预测价值。TMPRSS2-ERG具有预后价值，而PCA3不具有预后价值。将新型尿液生物标记物组合PCA3和TMPRSS2-ERG应用于临床将显著减少前列腺活检的数量。(C)2012年欧洲泌尿外科协会。爱思唯尔出版，版权所有。
Background: Prostate cancer antigen 3 (PCA3) and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG) gene fusions are promising prostate cancer (PCa) specific biomarkers that can be measured in urine.Objective: To evaluate the diagnostic and prognostic value of Progensa PCA3 and TMPRSS2-ERG gene fusions (as individual biomarkers and as a panel) for PCa in a prospectivemulticentre setting.Design, setting, and participants: At six centres, post-digital rectal examination first-catch urine specimens prior to prostate biopsies were prospectively collected from 497 men. We assessed the predictive value of Progensa PCA3 and TMPRSS2-ERG (quantitative nucleic acid amplification assay to detect TMPRSS2-ERG messenger RNA [mRNA]) for PCa, Gleason score, clinical tumour stage, and PCa significance (individually and as a marker panel). This was compared with serum prostate-specific antigen and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator. In a subgroup (n = 61) we evaluated biomarker association with prostatectomy outcome.Outcome measurements and statistical analysis: Univariate and multivariate logistic regression analysis and receiver operating curves were used.Results and limitations: Urine samples of 443men contained sufficientmRNAformarker analysis. PCa was diagnosed in 196 of 443 men. Both PCA3 and TMPRSS2-ERG had significant additional predictive value to the ERSPC risk calculator parameters in multivariate analysis (p < 0.001 and resp. p = 0.002). The area under the curve (AUC) increased from 0.799 (ERSPC risk calculator), to 0.833 (ERSPC risk calculator plus PCA3), to 0.842 (ERSPC risk calculator plus PCA3 plus TMPRSS2ERG) to predict PCa. Sensitivity of PCA3 increased from68% to 76% when combinedwith TMPRSS2ERG. TMPRSS2-ERGadded significant predictive value to the ERSPC risk calculator to predict biopsy Gleason score (p < 0.001) and clinical tumour stage (p = 0.023), whereas PCA3 did not.Conclusions: TMPRSS2-ERG had independent additional predictive value to PCA3 and the ERSPC risk calculator parameters for predicting PCa. TMPRSS2-ERG had prognostic value, whereas PCA3 did not. Implementing the novel urinary biomarker panel PCA3 and TMPRSS2-ERG into clinical practice would lead to a considerable reduction of the number of prostate biopsies. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.