Harvard/Michigan/Cornell Prostate Cancer Biomarker Clinical Validation Center

描述（由申请人提供）：我们的EDRN-CVC旨在提高前列腺癌的检测。在我们的第一个资助周期中，我们在活检前收集了1811名男性的血液标本，并领导了2项EDRN范围内的前列腺癌研究：1)在活检前收集了669名患有或没有前列腺癌的男性的EDRN前列腺癌血液标本参考集（运送到NCI的40万份血液标本）（69%的队列是在我们的CVC中累积的）；霍普金斯BRL验证了队列质量，在proPSA验证研究中使用了3000个等分，为FDA注册铺平了道路；2)在10个临床站点进行EDRN尿液PCA3试验，以检测PCA3对前列腺癌的预测，并在NCI-Frederick建立前列腺癌尿液参考集。与LaBaer的BLD合作，我们评估了前列腺癌自身抗体，但发现其患病率太低，无法产生临床影响。在Chinnaiyan BDL发现TMPRSS2:ERG融合（T-erg）后，我们转移了焦点：我们的CVC病理学家开发了一种FISH检测方法，用于在46%的前列腺癌活检中检测T-erg融合，并在瑞典队列中显示融合与致命进展相关。我们的CVC能够检测DRE后收集的尿液中的T-erg，并且我们将尿液T-erg、PCA3和血清PSA结合起来，在预测癌症方面优于单独的PSA （AUC为0.75 vs .58）。我们假设T-erg检测可以减轻PSA筛查的问题。我们建议：1)前瞻性验证尿Terg在预测前列腺癌诊断的多重模型中的性能，该模型预测了900名前列腺活检前收集的dre后尿液。2)在社区外展男性健康倡议中，以社区为基础的840名男性（包括420名非洲裔美国人）为样本，确定T-erg在非裔美国男性中的患病率。3)比较dre后尿T-erg检测与活检FISH检测融合的准确性。4)在CVC进行主动监测的300名男性中，为了测试Terg是否能区分纵向进展性癌症和惰性癌症，并将推迟治疗的300名男性（来自卫生专业人员随访研究）的前列腺活检组织带到EDRN进行II期验证。5)与bdl、brl、CVCs合作，评估和验证其他新的前列腺癌蛋白、RNA和SNP生物标志物。

DESCRIPTION (provided by applicant): Our EDRN-CVC aims to improve prostate cancer detection. In our first funding cycle, we collected blood specimens from 1811 men before biopsy and led 2 EDRN-wide prostate cancer studies:1) The EDRN Prostate Cancer Blood Specimen Reference Set (>40,000 blood specimen aliquots shipped to the NCI) collected before biopsy in 669 men with or without prostate cancer (69% of the cohort was accrued at our CVC); cohort quality was verified by Hopkins BRL that used 3000 of the aliquots in proPSA validation study paving the way for FDA registration; 2) The EDRN Urine PCA3 trial at 10 clinical sites to test PCA3 prediction of prostate cancer and establish a Prostate Cancer Urine Reference Set at NCI-Frederick. Collaborating with LaBaer's BLD, we evaluated prostate cancer auto-antibodies but found their prevalence too low for clinical impact. After the Chinnaiyan BDL discovered TMPRSS2:ERG fusion (T-erg) we shifted focus: Our CVC Pathologist developed a FISH assay we used to detect T-erg fusion in 46% prostate cancers on biopsy, and in a Swedish cohort showed fusion association with lethal progression. Our CVC enabled assays to detect T-erg in urine collected after DRE, and we combined urine T-erg, PCA3 and serum PSA to outperform PSA alone in predicting cancer (AUC 0.75 vs .58). We hypothesize that T-erg detection can mitigate problems of PSA screening. We propose: 1) To prospectively validate the performance of urinary Terg in a multiplex model predicting prostate cancer diagnosis in 900 men with post-DRE urine collected prior to prostate biopsy. 2) To determine T-erg prevalence among African-American men in a community-based sample of 840 men (including 420 African Americans) in a community outreach men's health initiative. 3) To compare accuracy of detecting T-erg in post-DRE urine to detecting the fusion by biopsy FISH. 4) To test if Terg discerns longitudinally progressive from indolent cancer in 300 men on active surveillance at our CVC, and bring to EDRN prostate biopsy tissue from a national cohort of 300 men who deferred treatment (from Health Professionals Follow-up Study) for Phase II validation. 5) To Collaborate with BDLs, BRLs, CVCs to evaluate and validate other new protein, RNA and SNP biomarkers of prostate cancer.