Evaluation of Predictive Signatures of Prostate Cancer

前列腺癌预测特征的评估

• 批准号: 6933551
• 负责人: Dan Mercola
• 金额: $ 170.71万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6933551
• 关键词: Evaluation; Predictive; Signatures; Prostate; Cancer

DESCRIPTION (provided by applicant): Prostate cancer is the most common malignancy of men in the U.S. and there is an urgent need to develop signatures that distinguish clinically significant disease with life threatening potential from the more common "indolent disease". We have developed methods for determining cell-specific gene expression of prostate carcinoma for four major cell types or groups within prostate carcinoma, including tumor cells, BPH, stroma, and cystic atrophy, and have identified over 3900 genes that are uniformly expressed in one cell type or another. The approach has been extended to identify ~1100 genes specifically associated with relapse as a surrogate for aggressive prostate cancer. These genes are lists by bioinformatics (Aim 1) and experimental methods (Aims 2-4) to develop a predictive signature and to validate the signature in a prospective trial. A consortium of strategic partners will cooperate in completing this goal. We will work with Jeffrey Trent of TGen to analyze 100 fresh surgical samples by quantitative PCR for 200 prioritized genes (Aim 2). Strategic partners at the University of California at San Diego and at Irvine will supplement the SKCC/Sharp HealthCare collection of clinically annotated paraffin blocks of prostate cancer to complete a current project to make a 1000 case tissue microarray (TMA). This TMA will be examined with 200 prioritized antibodies, manufactured by a commercial strategic partner, in cooperation with John Reed of the Burnham Institute (Aim 3). These arrays are specifically designed to (i) correlate gene expression with survival in a retrospective study, (ii) test whether stroma specific genes are correlated with adverse clinical outcomes, and (iii) whether tissue removed prior to the development of prostate cancer expresses predictive genes. Genes that are successfully validated by these methods will be utilized in a prospective observational clinical trial to be carried out at three sites (the Northwestern University Medical School Prostate SPORE, UCSD, and SKCC/Sharp HealthCare) to test the ability of the signatures to accurately predict early relapse (Aim 4). Changes in genes that are predictive of clinically relevant events will have strong justification for further development as predictive biomarkers.

描述（由申请人提供）： 前列腺癌是美国男性最常见的恶性肿瘤，迫切需要开发特征来区分具有威胁生命潜力的临床显着疾病和更常见的“惰性疾病”。我们开发了确定前列腺癌内四种主要细胞类型或细胞群（包括肿瘤细胞、BPH、基质和囊性萎缩）的前列腺癌细胞特异性基因表达的方法，并鉴定了在一种细胞中均匀表达的 3900 多个基因类型或其他。该方法已扩展到识别约 1100 个与复发特别相关的基因，作为侵袭性前列腺癌的替代物。这些基因通过生物信息学（目标 1）和实验方法（目标 2-4）列出，以开发预测特征并在前瞻性试验中验证该特征。战略合作伙伴联盟将合作完成这一目标。我们将与 TGen 的 Jeffrey Trent 合作，通过定量 PCR 分析 100 个新鲜手术样本中的 200 个优先基因（目标 2）。加州大学圣地亚哥分校和欧文分校的战略合作伙伴将补充 SKCC/Sharp HealthCare 收集的临床注释的前列腺癌石蜡块，以完成当前的项目，制作 1000 例组织微阵列 (TMA)。该 TMA 将使用 200 种优先抗体进行检查，这些抗体由商业战略合作伙伴与伯纳姆研究所的 John Reed 合作生产（目标 3）。这些阵列专门设计用于（i）在回顾性研究中将基因表达与生存相关联，（ii）测试基质特异性基因是否与不良临床结果相关，以及（iii）在前列腺癌发展之前去除的组织是否表达预测性的基因。通过这些方法成功验证的基因将用于在三个地点（西北大学医学院前列腺 SPORE、UCSD 和 SKCC/Sharp HealthCare）进行的前瞻性观察性临床试验，以测试签名准确预测的能力。预测早期复发（目标 4）。预测临床相关事件的基因变化将有充分理由进一步开发为预测生物标志物。