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.

知识的差距：目前没有准确的非侵入性测试可以在血尿患者中进行统治 或需要浸润性膀胱镜检查以评估膀胱的存在的膀胱癌病史（BCA） 瘤。背景：BCA患者最常见的症状是血尿。在两个大 研究，〜11％的血尿患者被发现携带BCA。已发布的指南建议这些 除膀胱镜评估外，患者要获得无效的尿细胞学（VUC）。膀胱镜是一个 与副作用相关的侵入性，不舒服且昂贵的程序，例如瞬态空隙 尿道的症状，血尿，UTI和狭窄，而VUC的敏感性有限25-40％ 检测BCA（特异性> 90％），尤其是对于低度和低阶段肿瘤。虽然有些商业 可用于检测BCA的可用基于尿液的测定法 与VUC相比（例如NMP-22和BTA）相比。此外，作为单个标记，这些测定法 包括VUC在内的预测能力不足，无法应用于单个患者的管理，并且 重要的是，这些技术很复杂，需要熟练的解释。我们目前的NIH/NCI R01 应用正在测试多重电化学发光（MEC）免疫测定能够检测我们的BCA-的能力 来自血液毛的受试者的无效尿液样本中的相关诊断签名，受试者和患者 BCA在肿瘤监测中的历史。自R01应用程序成立以来，我们已经开发了 验证了基于多重珠的（MBB）免疫测定，具有改进的操作特征 例如接收器操作特征下的面积，灵敏度和特异性（0.942：CI 0.8645 - 0.9627， 分别使用MBB平台和0.892：CI 0.850-0.934，85％和81％，分别使用93％和95％ MEC平台）。由于MBB分析的大幅改进，我们试图纳入 将MBB测定法评估为当前R01赠款，因此将MBB测定法与MEC进行比较 在此补充应用中进行测定。假设：MBB分析比 MEC测定在未经尿液样品中检测我们与BCA相关的诊断签名。方法：AS 使用MEC分析，我们将在CLIA认证的实验室中执行MBB测定法。然后，我们将比较和 对比MBB和MEC分析的运行特征在电流大型中心中 前瞻性研究。拟议的工作完成后，我们希望表明MBB分析不是 - 在检测我们的BCA签名时，低于MEC测定法。因此，MBB测定将过渡到 实验室并用于我们的后续研究，其最终目标是加速翻译的步伐 我们的NCI支持的方法/测定/技术/技术是诊所的前提，这是Par-17-003的前提。