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无创空尿检测提高对膀胱癌的一种常见人类癌症的检测。膀胱癌是男性中第四大最常见的癌症，也是第五大最常见的癌症，2008年美国大约有68,800个新病例和14,100人死于该疾病。据估计，在美国有近30万患者通过各种无创（尿液）和微创（膀胱穿刺、膀胱镜检查和活检）技术进行定期监测。因此，开发能够无创检测膀胱肿瘤的新型生物标志物具有重要的临床意义。在这项拨款中，我们建议在多机构验证方案中验证aurora A FISH测试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检测与其他已知的无创膀胱癌检测方法的特异性和敏感性，如尿细胞学和市售的多染色体FISH试剂盒UroVysion，以及NMP22护理点检测。本提案的具体目标如下：具体目标1：确定Aurora A FISH测试的可重复性。具体目标2：验证血尿患者BC检测模型，并确定Aurora a FISH和/或UroVysion FISH是否改进了该模型。将验证先前描述的包含临床变量和NMP22的nomogram。此外，Aurora A FISH和UroVysion FISH测试将评估其改善当前nomogram的能力。特异性目的3：确定Aurora A FISH检测BC的能力，并通过细胞学、UroVysion FISH和NMP22确定其性能。将确定极光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NMP22进行比较，并探索组合标记物提高检测的能力。特异性目的4：确定Aurora A FISH检测肿瘤进展高风险的BC患者的能力。Aurora A FISH的性能将与细胞学、UroVysion FISH和NMP22的性能进行比较。

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.