VALIDATION OF A MULTIPLEXED ASSAY FOR BLADDER CANCER DIAGNOSIS

膀胱癌诊断多重检测的验证

• 批准号: 9974986
• 负责人: Charles J Rosser
• 金额: $ 25.05万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974986
• 关键词: Adopted; Area; Biological Assay; Biological Markers; Bladder; Bladder Neoplasm; CLIA certified; Cancer Detection; Cells; Characteristics; Clinic; Clinical; Clinical Research; Complex; Cystoscopy; Cytogenetics; Cytology; Data; Detection; Diagnosis; Diagnostic; Evaluation; Fluorescent Antibody Technique; Goals; Gold; Grant; Guidelines; Head; Hematuria; Hemorrhage; Image; Immunoassay; Knowledge; Laboratories; Laboratory Research; Malignant neoplasm of urinary bladder; Methodology; Methods; Multi-Institutional Clinical Trial; Multicenter Studies; Non-Invasive Cancer Detection; Parents; Pathologist; Patients; Physicians; Procedures; Prospective Studies; Publishing; Receiver Operating Characteristics; Recording of previous events; Reporting; Sampling; Scientist; Sensitivity and Specificity; Specificity; Standardization; Stenosis; Symptoms; System; Techniques; Technology; Testing; Translations; Tumor stage; United States National Institutes of Health; Urethra; Urinary tract; Urinary tract infection; Urine; Visualization; Work; base; cancer diagnosis; diagnostic assay; improved; individual patient; next generation sequencing; prospective; research and development; side effect; tool; tumor; urinary

Gap in Knowledge: No accurate, non-invasive tests are currently available to rule in patients with hematuria or a history of bladder cancer (BCa) who need an invasive cystoscopy to evaluate the presence of a bladder tumor. Background: The most common presenting symptom in patients with BCa is hematuria. In two large studies, ~11% of patients with hematuria were noted to harbor 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. Our current NIH/NCI R01 application is testing a multiplex electrochemoluminescent (MEC) immunoassay’s ability to detect our BCa- associated diagnostic signature in voided urine samples from subjects with gross hematuria and subjects with a history of BCa on tumor surveillance. Since the inception of the R01 application, we have developed and validated a multiplex bead-based (MBB) immunoassay, which possesses improved operational characteristics such as area under receiver operating characteristic, sensitivity and specificity (0.942: CI 0.8645 – 0.9627, 93% and 95%, respectively using MBB platform vs. 0.892: CI 0.850 - 0.934, 85% and 81%, respectively using MEC platform). Because of the substantial improvement in the MBB assay, we seek to incorporate the evaluation of the MBB assay into the current R01 grant, and therefore compare the MBB assay to the MEC assay in this supplemental application. Hypothesis: The MBB assay is more sensitive and specific than the MEC assay in detecting our BCa-associated diagnostic signature in voided urine samples. Methodology: As with the MEC assay, we will perform the MBB assay in a CLIA-certified laboratory. We will then compare and contrast the operational characteristics of the MBB and MEC assays in the current, large multi-center prospective studies. Upon completion of the proposed work, we expect to show that the MBB assay is non- inferior to the MEC assay in detecting our BCa signature. Therefore, MBB assay will be transitioned into the laboratory and used for our subsequent studies with the ultimate goal of accelerating the pace of translation of our NCI-supported methods/assays/technologies to the clinic, which is the premise of PAR-17-003.

知识差距：目前没有准确的、非侵入性的测试来诊断血尿患者 或有膀胱癌 (BCa) 病史，需要进行侵入性膀胱镜检查来评估膀胱的存在 背景：BCa 患者最常见的症状是血尿。 研究发现，约 11% 的血尿患者存在 BCa。已发布的指南建议采用这些方法。 除了膀胱镜检查之外，患者还需要进行排尿细胞学检查（VUC）。 侵入性、不舒服且昂贵的手术，并伴有短暂性排尿等副作用 症状、血尿、UTI 和尿道狭窄，而 VUC 在以下情况中的敏感性有限：25-40% 检测BCa（特异性> 90％），特别是对于低级别和低阶段肿瘤，而一些商业化。 已有用于检测 BCa 的基于尿液的检测方法可用，但许多方法的检测量有所减少 与 VUC（例如 NMP-22 和 BTA）相比，这些检测具有特异性。 包括 VUC 的预测能力不足以应用于个体患者的管理，以及 重要的是，这些技术很复杂，需要我们当前的 NIH/NCI R01 熟练的解释。 应用程序正在测试多重电化学发光 (MEC) 免疫分析检测我们的 BCa- 的能力 肉眼血尿受试者和患有肉眼血尿的受试者的排尿样本中的相关诊断特征 BCa 在肿瘤监测方面的历史 自 R01 应用开始以来，我们已经开发并实施了该技术。 验证了多重微珠 (MBB) 免疫测定法，该测定法具有改进的操作特性 例如接受者操作特征下的面积、灵敏度和特异性（0.942：CI 0.8645 – 0.9627， 使用 MBB 平台分别为 93% 和 95% vs. 0.892：CI 0.850 - 0.934、使用时分别为 85% 和 81% MEC 平台）由于 MBB 测定的显着改进，我们寻求合并 将 MBB 测定纳入当前 R01 拨款的评估，因此将 MBB 测定与 MEC 进行比较 本补充申请中的测定：MBB 测定比 MBB 测定更灵敏、更特异。 MEC 检测在排空尿液样本中检测 BCa 相关诊断特征的方法：如。 对于 MEC 检测，我们将在 CLIA 认证的实验室中进行 MBB 检测，然后我们将进行比较和比较。 对比当前大型多中心中 MBB 和 MEC 检测的操作特性 前瞻性研究完成后，我们期望表明 MBB 测定是非- 在检测我们的 BCa 特征方面不如 MEC 测定，因此，MBB 测定将转变为 MEC 测定。 实验室并用于我们后续的研究，最终目标是加快翻译步伐 我们将 NCI 支持的方法/测定/技术应用于临床，这是 PAR-17-003 的前提。