MULTIPLEXED PROTEIN BIOMARKER-BASED ASSAY FOR THE DETECTION OF BLADDER CANCER

用于检测膀胱癌的多重蛋白质生物标志物检测

• 批准号: 9922223
• 负责人: Charles J Rosser
• 金额: $ 65.25万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2021-08-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922223
• 关键词: Adopted; Biological Assay; Biological Markers; Bladder; Bladder Neoplasm; Cancer Center; Clinic; Clinical; Clinical Trials; Complex; Cystoscopy; Cytogenetics; Cytology; Detection; Diagnosis; Diagnostic; Evaluation; FDA approved; Fluorescent Antibody Technique; Gold; Grant; Guidelines; Hematuria; Hemorrhage; Image; Immunoassay; Laboratory Scientists; Lead; Malignant neoplasm of urinary bladder; Measurement; Methodology; Microscopic; Molecular Profiling; Outcome; Patients; Physicians; Procedures; Publishing; Reporting; Risk; Sampling; Scientist; Site; Specificity; Standardization; Stenosis; Structure; Symptoms; Techniques; Technology; Testing; Tumor stage; Urethra; Urinary tract; Urine; Validation; Viral; Visualization; base; cancer diagnosis; cohort; cost effective; diagnostic assay; gastrointestinal; individual patient; pathogen; prospective; protein biomarkers; prototype; research and development; respiratory; side effect; tool; tumor; urinary; validation studies

Project Summary/Abstract Background The most common presenting symptom in patients with bladder cancer is hematuria. In two large studies, 5-8% of patients with microscopic hematuria (> 3 RBC/hpf) were noted to harbor bladder cancer (BCa). Published guidelines recommend these patients to obtain voided urinary cytology (VUC), in addition to cystoscopic evaluation. Cystoscopy is an invasive, uncomfortable and expensive procedure associated with side effects such as transient voiding symptoms, hematuria, UTI, and stenosis of the urethra, whereas, VUC has limited sensitivity of 25-40% in detecting BCa (specificity is >90%), especially for low-grade and low-stage tumors. While some commercially available urine-based assays for the detection of BCa are available, many suffer from a reduction in assay specificity compared to VUC (e.g., NMP-22 and BTA). Furthermore, as single markers, these assays, including VUC have insufficient predictive power to be applied to the management of individual patients, and importantly, these techniques are complex, and require skillful interpretation. The clinical impact of the proposal is to develop a more reliable and standardize assay that can detect BCa using a voided urine sample. Premise Our central premise is that our bladder cancer (BCa)- associated diagnostic signature may be successfully adopted to a multiplex bead-based immunoassay platform and utilized for the detection of BCa. Specific Aims: Specific Aim #1: To refine our prototype multiplex bead-based immunoassay such that it is enhanced for our ongoing prospective, multicenter validation studies. Significance If validated, the assay will be incorporated in the current R01 and could ultimately lead to a reduction in the need to subject large numbers of patients who do not have BCa to frequent, uncomfortable and expensive cystoscopic examinations. Methodology We will refine and optimize the multiplex assay and then test it in two large cohorts. prior to being incorporated into the current clinical trials associated with the R01. Expected Results Within this project, we will transform our prototype multiplex bead-based immunoassay into the final multiplex bead-based immunoassay that has been analytically and clinically validated and thus poised to undergo external multiple site validation in the prospective clinical trials associated with the current R01 grant.

项目概要/摘要 背景 膀胱癌患者最常见的症状是血尿。分成两份 大型研究表明，5-8% 的镜下血尿 (> 3 RBC/hpf) 患者被发现患有膀胱癌 （BCa）。已发布的指南建议这些患者进行排空尿细胞学检查 (VUC)，此外 进行膀胱镜评估。膀胱镜检查是一种侵入性、不舒服且昂贵的手术，与 副作用，如短暂排尿症状、血尿、UTI 和尿道狭窄，而 VUC 检测 BCa 的灵敏度有限，为 25-40%（特异性 >90%），特别是对于低级别和低阶段 肿瘤。虽然可以使用一些市售的基于尿液的 BCa 检测方法， 与 VUC（例如 NMP-22 和 BTA）相比，许多检测特异性降低。此外， 作为单一标记物，这些检测（包括 VUC）的预测能力不足以应用于 管理个别患者，重要的是，这些技术很复杂，并且需要熟练的 解释。该提案的临床影响是开发一种更可靠和标准化的检测方法，可以 使用排空的尿液样本检测 BCa。前提 我们的中心前提是我们的膀胱癌 (BCa)- 相关的诊断特征可以成功地应用于基于多重微珠的免疫测定 平台并用于BCa的检测。具体目标：具体目标#1：完善我们的原型 基于多重珠子的免疫测定，使其针对我们正在进行的前瞻性、多中心 验证研究。意义 如果得到验证，该检测将被纳入当前的 R01 中，并且可以 最终减少大量没有 BCa 的患者接受治疗的需要 频繁、不舒服且昂贵的膀胱镜检查。方法论 我们将细化和优化 多重测定，然后在两个大组中进行测试。在纳入当前临床之前 与 R01 相关的试验。预期结果 在这个项目中，我们将改造我们的多路复用原型机 基于珠子的免疫分析最终的多重基于珠子的免疫分析已经过分析和验证 经过临床验证，因此准备在前瞻性临床试验中进行外部多中心验证 与当前的 R01 拨款相关。