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临床表现是血尿。分成两份 大型研究发现，镜检血尿患者中有5-8%患有膀胱癌。 (BCA)。已公布的指南建议这些患者进行尿液细胞学检查(VUC)，此外 到膀胱镜检查。膀胱镜检查是一种侵入性、不适和昂贵的手术，与 副作用，如一过性排尿症状、血尿、尿路感染和尿路狭窄，而VUC 对BCA的敏感性有限，仅为25%-40%(特异性为90%)，特别是对低级别和低分期的患者 肿瘤。虽然一些商业上可用的基于尿液的检测BCA的分析是可用的， 与VUC(例如，NMP-22和BTA)相比，许多人的检测特异性降低。此外， 作为单一标记物，这些分析，包括VUC，不足以应用于 对个别患者的管理，重要的是，这些技术很复杂，需要熟练的 释义。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 用排空的尿样检测BCA。前提我们的中心前提是我们的膀胱癌- 相关诊断特征可成功地应用于基于微珠的多重免疫分析 并用于BCA的检测。具体目标：具体目标1：改进我们的原型 基于多重珠粒的免疫分析，以便为我们正在进行的预期的多中心增强 验证性研究。意义如果得到验证，该检测将被纳入当前的R01，并可能 最终减少了使大量没有BCA的患者接受 频繁、不舒服和昂贵的膀胱镜检查。我们将改进和优化方法 进行多重检测，然后在两个大的队列中进行测试。在被并入当前的临床 与R01相关的试验。预期结果在这个项目中，我们将转换我们的原型多路 将基于微珠的免疫分析引入最终的基于微珠的多重免疫分析，该分析和 临床验证，并因此准备在前瞻性临床试验中接受外部多部位验证 与当前的R01拨款相关联。