Biomarker Development Laboratory

主动监测（AS），即推迟对低风险PCa患者的治疗，直到出现进展迹象。 通过仔细监测发现，作为一种潜在的解决方案，以减少过度治疗低， 有患癌症的危险。对于这种BCC/BDL，我们建议开发多模式生物标志物组和相关的体外研究。 用于两种特定临床预期用途的诊断性多变量指数测定（IVDMIA）， AS的有效性：1）IVDMIA使用血清、尿液和活检组织生物标志物来识别低血糖患者 风险PCa从那些侵略性疾病，和/或提供准确的临床分级和分期，以帮助 AS入组;和2）非侵入性（血清和尿液）生物标志物的IVDMIA，以灵敏地检测AS的早期体征。 疾病重新分类，确定性治疗有临床意义的提前期。为了开发这些生物标志物 我们提出了四个具体目标。目标1。进行整合蛋白质组和糖蛋白质组 表征多模式临床标本，以重新发现和开发生物标志物， 整合现有的生物标志物或来自我们目前的BDL/BRL的生物标志物，用于两种特定的预期用途;目标2。工作 与我们BCC的BRL组件一起开发高质量的检测方法，以准确有效地评估 选择的候选生物标志物;目标3.（与BRL共同目标）开发和评价IVDMIA，以实现临床 预定义临床用途的有意义的性能特征;以及目标4。参加EDRN 网络研究项目，包括积极参与和促进正在进行的和未来的网络 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），负责研究方向、数据和结果报告 准则/标准和一般工作协调。BDL的创新包括独特的目标AS人群， 用于生物标志物发现和预验证的最先进的蛋白质组学和糖蛋白质组学技术 阶段，用于检测特定修饰蛋白质形式的免疫测定，组织定量分析 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整合现有临床 并将疾病的生物学知识转化为定量分析的发现和IVDMIA模型 通过单细胞分析和批量表达对PCa蛋白质组进行优化和确证分析 数据反褶积总之，拟议的BCC/BDL已经收集了一系列独特的油井， 代表预期目标人群的特征化多模式生物样本采集;以及 提出了一个明确的路径，使用最先进的和创新的蛋白质组学，糖蛋白质组学，统计学， 生物信息学方法用于IVDMIA的生物标志物发现和验证，以实现临床意义 两种明确定义的预期临床用途的性能，这对成功至关重要 前列腺癌的治疗方法

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.