Harvard/Michigan/Cornell Prostate Cancer Biomarker Clinical Validation Center

描述（由申请人提供）：我们的EDRN-CVC旨在改善前列腺癌检测。在我们的第一个资助周期中，我们在活检前收集了1811名男性的血液样本，并领导了2项EDRN范围内的前列腺癌研究：1）EDRN前列腺癌血液样本参考集在669名患有或不患有前列腺癌的男性中，在活检前收集的（> 40，000份血液样本等分试样运送到NCI）（69%的队列在我们的CVC累积）;队列质量由霍普金斯BRL验证，其在proPSA验证研究中使用3000个等分试样，为FDA注册铺平道路; 2）EDRN尿液PCA 3试验在10个临床站点测试前列腺癌的PCA 3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TMPRSS 2：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测定法，我们用于在活检时检测46%前列腺癌中的T-erg融合，并且在瑞典队列中显示融合与致死性进展相关。我们的CVC使检测DRE后收集的尿液中的T-erg成为可能，并且我们将尿液T-erg、PCA 3和血清PSA相结合，在预测癌症方面优于单独的PSA（AUC 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，该模型在900名男性中使用前列腺活检前收集的DRE后尿液。2)确定T-erg患病率在非洲裔美国男性在社区为基础的样本840名男性（包括420名非洲裔美国人）在社区外展男子的健康倡议。3)比较DRE后尿中T-erg检测与活检FISH检测融合的准确性。4)为了测试Terg是否在我们的CVC主动监测的300名男性中辨别出纵向进展性惰性癌症，并将来自推迟治疗的300名男性的国家队列（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，CVC合作，评估和验证其他新的前列腺癌蛋白质，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.