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

项目概要/摘要 背景膀胱癌患者最常见的临床症状是血尿。在两 在一项大型研究中，5-8%的镜下血尿（> 3 RBC/hpf）患者被发现患有膀胱癌 （BCa）。已发表的指南建议这些患者进行排尿细胞学检查（VUC），此外 膀胱镜检查膀胱镜检查是一种侵入性，不舒服和昂贵的程序， 副作用如短暂性排尿症状、血尿、UTI和尿道狭窄，而VUC 检测BCa的敏感性有限，为25-40%（特异性>90%），尤其是低级别和低阶段 肿瘤的虽然一些市售的用于检测BCa的基于尿的测定是可用的， 与VUC相比，许多人遭受测定特异性的降低（例如，NMP-22和BTA）。此外，委员会认为， 作为单一标志物，这些测定，包括VUC，没有足够的预测能力应用于 个体患者的管理，重要的是，这些技术是复杂的，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， 使用排出的尿液样本检测BCa。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用于基于多重珠的免疫测定 平台，并用于检测BCa。具体目标：具体目标1：完善我们的原型 多重珠为基础的免疫测定，使其增强我们正在进行的前瞻性，多中心， 验证研究。显著性如果经过验证，该检测试剂盒将纳入当前R 01中， 最终导致减少对大量没有BCa的患者的需求， 频繁、不舒服和昂贵的膀胱镜检查。方法我们将完善和优化 然后在两个大的队列中测试它。在被纳入当前的临床 与R 01相关的试验。在这个项目中，我们将把我们的原型多路复用器 将基于微珠的免疫测定转化为最终的多重基于微珠的免疫测定， 经过临床验证，因此准备在前瞻性临床试验中接受外部多中心验证 与当前R 01授权相关联。

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.