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.

项目摘要/摘要 背景膀胱癌患者最常见的症状是血尿。一两个 大型研究，有5-8％的微观血尿（> 3 rbc/hpf）被发现携带膀胱癌 （BCA）。已发表的指南建议这些患者获得无效的尿细胞学（VUC），此外 进行膀胱镜评估。膀胱镜检查是一种侵入性，不舒服且昂贵的程序 副作用，例如暂时空隙症状，尿道的血尿，UTI和狭窄，而VUC 在检测BCA（特异性> 90％）中的灵敏度有限为25-40％，尤其是对于低级和低阶段 肿瘤。尽管有一些可用于检测BCA的市售的基于尿液的测定法 与VUC（例如NMP-22和BTA）相比，许多人的特异性降低。此外， 作为单个标记，包括VUC在内的这些测定的预测能力不足以应用于 管理单个患者，重要的是，这些技术很复杂，需要熟练 解释。该提案的临床影响是开发更可靠和标准化的测定法 使用无效的尿液样品检测BCA。前提我们的中心前提是我们的膀胱癌（BCA） - 相关的诊断签名可以成功地用于基于多重珠的免疫测定 平台并用于检测BCA。具体目的：特定目标＃1：完善我们的原型 基于多重珠的免疫测定法可以增强我们正在进行的前瞻性，多中心 验证研究。如果经过验证，则该测定法会纳入当前R01，并且可以 最终导致需要减少大量没有BCA的患者 经常，不舒服且昂贵的膀胱镜检查。方法论我们将完善和优化 多路复用测定，然后在两个大同类群中进行测试。在纳入当前临床之前 与R01相关的试验。该项目中的预期结果，我们将改变我们的原型多路复用 基于珠的免疫测定到最终的多重珠的免疫测定法，该免疫测定已通过分析和 经过临床验证，并因此准备在前瞻性临床试验中接受外部多重位点验证 与当前R01赠款相关。