Biomarker Development Laboratory

主动监测(AS)，推迟对低风险PCA患者的治疗，直到出现进展迹象 通过仔细的监测发现，被开发为减少低分化症过度治疗的潜在解决方案。 冒着癌症的风险。对于这个bcc/bdl，我们建议开发多模式生物标志物面板并在体外相关 诊断多变量指数分析(IVDMIAs)用于两个特定的临床预期用途，以改善 AS的有效性：1)IVDMIAs使用血清、尿液和活检组织生物标记物来识别低... 从患有侵袭性疾病的人那里获得PCa风险，和/或提供准确的临床分级和分期，以帮助 作为登记；以及2)非侵入性(血清和尿液)生物标记物的IVDMIAs，以灵敏地检测早期症状 疾病重新分类，具有临床意义的最终治疗提前时间。开发这些生物标记物 在小组会议上，我们提出了四个具体目标。目的1.进行蛋白质组学和糖蛋白组学的整合 多模式临床标本的表征以发现和开发新的生物标记物以及 将现有的或来自我们目前的BDL/BRL的生物标记物整合到两个特定的预期用途；目标2.工作 与我们的BCC中的BRL组件一起开发高质量的检测方法，以准确高效地评估 选定的候选生物标记物；目标3.(与BRL共同瞄准)开发和评估IVDMIAs以实现临床 对预定义的临床用途有意义的性能特征；以及目标4.参与EDRN 网络研究项目，包括积极参与正在进行的和未来的网络并为其做出贡献 项目，与其他BCC和CVC合作，并与EDRN领导层、执行委员会和 数据管理和协调中心(DMCC)关于研究方向、数据和结果报告 标准/标准，以及总体努力协调。BDL的创新包括独特的目标人群， 用于生物标记物发现和预验证的最新蛋白质组和糖蛋白组学技术 阶段，检测特定修饰蛋白形式的免疫分析，组织的定量分析 通过单细胞分析和免疫组织化学染色以及使用 液体组织测量。创新的生物信息学方法包括结合现有临床 并将生物学知识纳入量化分析，用于发现和IVDMIA模型 基于单细胞分析和批量表达的PCA蛋白质组优化及验证分析 数据去卷积。总而言之，拟议的BCC/BDL汇集了一系列独特的油井 代表预定目标人群的多模式生物样品收集的特点；以及 提出了一条使用最先进和创新的蛋白质组学、糖蛋白组学、统计学和 生物信息学方法用于发现和验证IVDMIA的生物标志物以实现临床意义 两个明确定义的预期临床用途的性能，这两个用途对成功至关重要 前列腺癌主动监测。

Active surveillance (AS), which holds off on treatment for low-risk PCa patients until signs of progression are detected through careful monitoring, was developed as a potential solution to decrease over-treatment of low- risk cancer. For this BCC/BDL, we propose to develop multimodal biomarker panels and associated in vitro diagnostic multivariate index assays (IVDMIAs) for two specific clinical intended uses to improve the effectiveness of AS: 1) IVDMIAs using serum, urine, and biopsy tissue biomarkers to identify patients with low- risk PCa from those with aggressive disease, and/or to provide accurate clinical grading and staging to assist in AS enrollment; and 2) IVDMIAs of non-invasive (serum and urine) biomarkers to sensitively detect early signs of disease reclassification with clinically meaningful lead time for definitive treatment. To develop these biomarker panels, we propose four specific aims. Aim 1. To perform integrated proteomic and glycoproteomic characterization of multimodal clinical specimens to discover and develop biomarkers de novo as well as integrate biomarkers existing or from our current BDL/BRL for the two specific intended uses; Aim 2. To work with the BRL component of our BCC to develop high-quality assays for accurate and efficient evaluation of selected candidate biomarkers; Aim 3. (co-Aim with BRL) To develop and evaluate IVDMIAs to achieve clinically meaningful performance characteristics for the predefined clinical uses; and Aim 4. To participate in EDRN network research projects, including actively participating in and contributing to on-going and future network projects, collaborate with other BCCs and CVCs, and work with EDRN leadership, Executive Committee, and Data Management and Coordinating Center (DMCC) regarding research direction, data and results report criteria/standards, and general effort coordination. Innovations of the BDL include unique targeted AS population, state-of-the-art proteomic and glycoproteomic technologies for both biomarker discovery and pre-validation phases, immunoassays for the detection of specific modified protein forms, quantitative analysis of tissue proteins by single-cell analysis and immunohistochemistry staining as well as quantitative measurement using liquid tissue measurement. Innovative bioinformatics approaches include tools that incorporate existing clinical and biological knowledge of the disease into the quantitative analysis for discovery and IVDMIA model optimization and corroborative analysis of the PCa proteome through single-cell analysis and bulk expression data deconvolution. In summary, the proposed BCC/BDL has assembled a unique collection of well characterized multimodal biospecimen collections representative of the intended targeted populations; and proposed a clear path using state-of-the-art and innovative proteomics, glycoproteomics, statistics, and bioinformatics approaches for biomarker discovery and validation of IVDMIAs to achieve clinically meaningful performance for the two clearly defined intended clinical uses that are critically important for the success of prostate cancer active surveillance.