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: 9267137
• 负责人: Charles J Rosser
• 金额: $ 59.53万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 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 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9267137
• 关键词: American; Biological Assay; Biological Markers; Bladder; Blood; Cancer Detection; Cancer Patient; Clinical Data; Complex; Cost Savings; Cystoscopy; Cytology; Data; Data Set; Detection; Diagnostic; Disease; Enzyme-Linked Immunosorbent Assay; European; Evaluation; Gene Expression; Gene Expression Profiling; Goals; Gold; Health Care Costs; Healthcare; Hematuria; Individual; Intervention; Investigation; Link; Longitudinal cohort; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measurement; Methodology; Methods; Microscopic; Modeling; Molecular; Molecular Profiling; Monitor; National Comprehensive Cancer Network; Outcome; Patient Care; Patients; Performance; Prospective cohort; Protocols documentation; Publishing; Recommendation; Recording of previous events; Recurrence; Research; Risk; Sampling; Specificity; Techniques; Testing; Time; Translating; Tumor stage; Urine; Urology; Validation; base; cohort; cost; design; disorder risk; improved; individual patient; innovation; molecular diagnostics; patient stratification; prospective; protein biomarkers; public health relevance; tumor; urinary; urologic

 DESCRIPTION (provided by applicant): Hematuria is the most common presentation of bladder cancer (BCa) with 22% of patients with gross hematuria and 8% of patients with microscopic hematuria harboring BCa. Voided urinary cytology (VUC) is the most widely used urine-based assay (and gold standard) for detecting BCa; however, it fails to detect approximately 50% of low-grade or early stage BCa when it is most curable. Furthermore, the detection rate of VUC for recurrent BCa is not much better. Because of this severe limitation, all patients with hematuria and who are under surveillance to monitor for recurrent BCa must undergo an invasive examination of the urinary bladder, where a miniature camera is inserted into the bladder and the bladder inspected. We propose to improve the detection of BCa by utilizing a multiplex ELISA for the detection of a previously validated BCa- associated diagnostic signature (signature) in voided urine. Hypothesis A molecular profile exists that a) is specificall associated with BCa and b) can be utilized to indicate the presence of BCa in non-invasively obtained voided urine samples. This hypothesis will be tested by completing the following Specific Aims: 1) To validate the multiplex ELISA for BCa detection in subjects presenting with gross hematuria, 2) To validate the multiplex ELISA for BCa detection in patients with a history of BCa currently undergoing tumor surveillance and 3) To investigate the ability of the BCa-associated diagnostic signature to determine risk of disease. Significance This research will open the door for improving on the non-invasive methods for detecting BCa and will have a marked impact on patient care. Methodology Our group has developed and tested a multiplex ELISA towards this signature. In this proposal, we will test the multiplex ELISA in 2 independent studies: patients presenting with gross hematuria and BCa patients undergoing tumor surveillance. Expected Results The validation of the multiplex ELISA will reduce the need to subject large numbers of patients who do not have BCa to frequent, uncomfortable and expensive cystoscopic examinations. Specifically, we would anticipate a reduction in the number of cystoscopies/year by 500,000, which would translate into cost savings of $225 million/year.

 描述(申请人提供)：血尿是膀胱癌(BCA)最常见的表现，22%的肉眼血尿患者和8%的镜检血尿患者存在BCA。尿液细胞学检查(VUC)是目前应用最广泛的尿液BCA检测方法(也是金标准)；然而，在最能治愈的情况下，它无法检测出约50%的低度或早期BCA。此外，VUC对复发性BCA的检出率也好不到哪里去。由于这一严重的局限性，所有有血尿的患者以及正在监测是否有复发的BCA的患者都必须接受膀胱的侵入性检查，在膀胱中插入微型摄像机并检查膀胱。我们建议通过利用多重酶联免疫吸附试验检测排尿中先前确认的BCA相关诊断特征(SIGN)来改进BCA的检测。假设A)存在分子图谱，即a)与BCA有关，b)可用来指示非侵入性获得的排空尿样中是否存在BCA。这一假设将通过完成以下具体目标来验证：1)验证用于肉眼血尿患者的BCA检测的多重ELISA法，2)验证用于有BCA正在接受肿瘤监测的患者的BCA检测的多重ELISA法，以及3)研究BCA相关的诊断特征确定疾病风险的能力。意义本研究将为改进BCA的非侵入性检测方法打开大门，并将对患者的护理产生显着影响。方法我们的团队已经开发并测试了一种针对该签名的多重ELISA。在这项提案中，我们将在两个独立的研究中测试多重ELISA：出现肉眼血尿的患者和接受肿瘤监测的BCA患者。预期结果多重ELISA法的验证将减少大量没有BCA的患者接受频繁、不适和昂贵的膀胱镜检查的需要。具体地说，我们预计每年膀胱镜检查的数量将减少50万次，这将转化为每年2.25亿美元的成本节约。