Aurora Kinase A as a Biomarker for the Detection of Bladder Cancer

描述（由申请人提供）：该项目的长期目标是通过非侵入性排尿检测来提高对膀胱中常见人类癌症之一的检测。膀胱癌是男性中第四常见的癌症，总体上第五常见，2008年在美国约有68，800例新发病例和14，100例死亡。据估计，在美国，通过各种非侵入性（尿液）和微创（膀胱穿刺术、膀胱镜检查和活检）技术定期监测近30万例患者。因此，开发新的生物标志物，可以通过非侵入性方法检测膀胱肿瘤具有重要的临床意义。在这项资助中，我们建议在多机构验证协议中验证极光A FISH检测作为膀胱癌检测的生物标志物。在本方案中，我们将比较aurora A FISH检测与其他已知的尿沉渣非侵入性膀胱癌检测检测的特异性和灵敏度，如尿细胞学和市售多染色体FISH试剂盒（称为UroVysion）和NMP 22即时检测。本提案的具体目标如下：具体目标1：确定Aurora A FISH检测的重现性。具体目标2：建立血尿患者BC检测模型，并确定Aurora A FISH和/或UroVysion FISH是否改善了模型。将验证先前描述的包含临床变量和NMP 22的列线图。此外，还将评估Aurora A FISH和UroVysion FISH检测改善当前列线图的能力。具体目标3：确定Aurora A FISH检测BC的能力，并确定其与细胞学、UroVysion FISH和NMP 22的性能。将确定Aurora A FISH的灵敏度和特异性。Aurora A FISH的性能将与细胞学、UroVysion FISH以及NMP 22进行比较，并将探索标记物组合改善检测的能力。具体目标4：确定Aurora A FISH检测肿瘤进展高风险BC患者的能力。Aurora A FISH性能将与细胞学、UroVysion FISH和NMP 22进行比较。

DESCRIPTION (provided by applicant): The long-term objective of this project is to improve the detection of one of the common human cancers arising in the bladder by non-invasive voided urine-based tests. Bladder cancer is the 4th most common cancer in men and 5th most common overall with an approximately 68,800 new cases and 14,100 deaths from the disease in 2008 in the United States. It is estimated that nearly 300,000 patients are regularly monitored in the United States through a variety of non-invasive (urine) and minimally invasive (bladder barbotage, cystoscopy, and biopsy) techniques. Therefore, the development of novel biomarkers that can detect bladder tumors by a non-invasive approach is of major clinical significance. In this grant we propose to validate aurora A FISH test as a biomarker for the detection of bladder cancer in the multi-institutional validation protocol. In this protocol, we will compare the specificity and sensitivity of aurora A FISH test with other known noninvasive bladder cancer detection tests for voided urine sediments such as urine cytology and commercially available multi-chromosomal FISH kit known as UroVysion, and NMP22 point-of-care test. The specific aims for this proposal are as follows: Specific Aim 1: Determine the reproducibility of the Aurora A FISH test. Specific Aim 2: Validate a model for BC detection in patients with hematuria and determine if Aurora A FISH and/or UroVysion FISH improves the model. A previously described nomogram incorporating clinical variables and NMP22 will be validated. Furthermore, the Aurora A FISH and UroVysion FISH tests will be assessed for their ability to improve the current nomogram. Specific Aim 3: Determine the ability of Aurora A FISH to detect BC and determine its performance with cytology, UroVysion FISH, and NMP22. The sensitivity and specificity of Aurora A FISH will be determined. The performance of Aurora A FISH will be compared with cytology, UroVysion FISH as well as NMP22 and the ability of a combination of markers to improve detection will be explored. Specific Aim 4: Determine the ability of Aurora A FISH to detect patients with BC who are at high risk of tumor progression. Aurora A FISH performance will be compared with that of cytology, UroVysion FISH, and NMP22.