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

 描述（由申请人提供）：血尿是膀胱癌（BCa）最常见的表现，22%的患者肉眼血尿，8%的患者镜下血尿携带BCa。排尿细胞学（VUC）是最广泛使用的尿液检测（和金标准），用于检测BCa;然而，它无法检测到约50%的低度或早期BCa时，它是最可治愈的。此外，VUC对复发性BCa的检出率并不高。由于这种严重的局限性，所有患有血尿并处于监测下以监测复发性BCa的患者都必须接受膀胱的侵入性检查，其中将微型摄像机插入膀胱并检查膀胱。我们提出通过利用多重ELISA检测排泄尿液中先前验证的BCa相关诊断特征（特征）来改善BCa的检测。假设A分子谱存在，a）与BCa特异性相关，并且B）可用于指示非侵入性获得的排泄尿液样品中BCa的存在。将通过完成以下特定目的来检验该假设：1）验证用于存在肉眼血尿的受试者中BCa检测的多重ELISA，2）验证用于目前正在接受肿瘤监测的具有BCa病史的患者中BCa检测的多重ELISA，以及3）研究BCa相关诊断特征确定疾病风险的能力。意义本研究将为改善BCa检测的非侵入性方法打开大门，并将对患者护理产生显着影响。我们的小组已经开发并测试了针对该特征的多重ELISA。在本提案中，我们将在2项独立研究中测试多重ELISA：肉眼血尿患者和接受肿瘤监测的BCa患者。预期结果多重ELISA的验证将减少对大量没有BCa的患者进行频繁、不舒服和昂贵的膀胱镜检查的需要。具体而言，我们预计膀胱镜检查的数量每年减少50万例，这将转化为每年2.25亿美元的成本节约。

 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.