Harvard/Michigan/Cornell Prostate Cancer Biomarker Clinical Validation Center

描述(申请人提供)：我们的EDRN-CVC旨在提高前列腺癌的检测能力。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范围的前列腺癌研究：1)EDRN前列腺癌血液样本参考集(&gt；40,000份等份血液样本运往NCI)，在669名患有或不患有前列腺癌的男性(69%在我们的CVC获得)活检前收集；队列质量由Hopkins BRL验证，该中心在ProPSA验证研究中使用了3000份等量样本，为FDA的注册铺平了道路；2)EDRN尿液PCA3试验在10个临床地点进行，以测试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，但发现它们的患病率太低，无法产生临床影响。在Chinnaiyan BDL发现TMPRSS2：ERG融合(T-ERG)后，我们转移了重点：我们的CVC病理学家开发了一种FISH分析，我们用来检测46%的活检前列腺癌T-ERG融合，在瑞典的一个队列中显示融合与致命进展相关。我们的CVC能够检测DRE后收集的尿中T-ERG，我们结合尿T-ERG、PCA3和血清PSA在预测癌症方面优于单独PSA(AUC 0.75比.58)。我们假设T-ERG检测可以缓解PSA筛查的问题。我们建议：1)前瞻性地验证尿TERG在预测前列腺癌诊断的多重模型中的表现，该模型对900名在前列腺活检前收集DRE后尿液的男性进行预测。2)在社区外展男性健康倡议中，对840名男性(包括420名非裔美国人)进行社区抽样，以确定T-ERG在非裔美国人中的患病率。3)比较DRE术后尿T-erg检测与FISH检测融合的准确性。4)在我们CVC积极监测的300名男性中，测试TERG是否识别出惰性癌症的纵向进展，并将300名推迟治疗(来自Health Professional后续研究)的全国队列中的前列腺活检组织带到EDRN进行II期验证。5)与BDLS、BRL、CVCS合作，评估和验证前列腺癌的其他新的蛋白质、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.