前瞻性多中心研究 PCA3 和 TMPRSS2-ERG 基因融合作为前列腺癌的诊断和预后尿液生物标志物。
Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer.
机构信息
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, The Netherlands.
Noviogendix, Department of Research and Development, Nijmegen, The Netherlands.
出版信息
Eur Urol. 2014 Mar;65(3):534-42. doi: 10.1016/j.eururo.2012.11.014. Epub 2012 Nov 15.
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 prospective multicentre 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 443 men contained sufficient mRNA for marker 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 TMPRSS2-ERG) to predict PCa. Sensitivity of PCA3 increased from 68% to 76% when combined with TMPRSS2-ERG. TMPRSS2-ERG added 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.
背景
前列腺癌抗原 3（PCA3）和 v-ets 红细胞生成病毒 E26 癌基因同系物（TMPRSS2-ERG）基因融合是有前途的前列腺癌（PCa）特异性生物标志物，可以在尿液中测量。
目的
在一个前瞻性多中心环境中，评估 Progensa PCA3 和 TMPRSS2-ERG 基因融合（作为单个生物标志物和作为一个标志物面板）在 PCa 中的诊断和预后价值。
设计、设置和参与者：在六个中心，在进行前列腺活检之前，通过数字直肠检查后首次采集的尿液标本，前瞻性地收集了 497 名男性的尿液标本。我们评估了 Progensa PCA3 和 TMPRSS2-ERG（定量核酸扩增检测以检测 TMPRSS2-ERG 信使 RNA [mRNA]）对 PCa、Gleason 评分、临床肿瘤分期和 PCa 意义（单独和作为标志物面板）的预测价值。这与血清前列腺特异性抗原和欧洲前列腺癌筛查研究（ERSPC）风险计算器进行了比较。在一个亚组（n=61）中，我们评估了生物标志物与前列腺切除术结果的关联。
测量和统计分析结果
使用单变量和多变量逻辑回归分析和接收器操作曲线。
结果和局限性
尿液样本中 443 名男性的 mRNA 含量足以进行标志物分析。在 443 名男性中，196 名被诊断为 PCa。在多变量分析中，PCA3 和 TMPRSS2-ERG 均具有显著的附加预测价值（p<0.001 和分别为 p=0.002）。曲线下面积（AUC）从 0.799（ERSPC 风险计算器）增加到 0.833（ERSPC 风险计算器加 PCA3），再增加到 0.842（ERSPC 风险计算器加 PCA3 加 TMPRSS2-ERG）以预测 PCa。当与 TMPRSS2-ERG 联合使用时，PCA3 的灵敏度从 68%增加到 76%。TMPRSS2-ERG 对 ERSPC 风险计算器预测活检 Gleason 评分（p<0.001）和临床肿瘤分期（p=0.023）具有显著的附加预测价值，而 PCA3 则没有。
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，可用于预测 PCa。TMPRSS2-ERG 具有预后价值，而 PCA3 则没有。将新型尿液生物标志物面板 PCA3 和 TMPRSS2-ERG 引入临床实践将导致前列腺活检数量的大量减少。
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