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.
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 and compare it with urine cytology, UroVysion FISH, and NMP22 tests. Given the high frequency of bladder cancer, the development of a specific and sensitive test for the disease by a non-invasive approach will have a great impact on its cost effective management. The clinical use of such a test will represent a novel standard of practice facilitating early treatment of bladder cancer and positively affecting the survival rates of the patients with bladder cancer.
|Dadhania, Vipulkumar; Zhang, Miao; Zhang, Li et al. (2016) Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use. EBioMedicine 12:105-117|
|Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W et al. (2014) Bladder cancer biomarker discovery using global metabolomic profiling of urine. PLoS One 9:e115870|
|Choi, Woonyoung; Porten, Sima; Kim, Seungchan et al. (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152-65|
|Tran, Mai N; Choi, Woonyoung; Wszolek, Matthew F et al. (2013) The p63 protein isoform Î”Np63Î± inhibits epithelial-mesenchymal transition in human bladder cancer cells: role of MIR-205. J Biol Chem 288:3275-88|
|Lee, Sangkyou; Lee, Ilkyun; Jung, Yoonsuh et al. (2012) In-frame cDNA library combined with protein complementation assay identifies ARL11-binding partners. PLoS One 7:e52290|
|Majewski, Tadeusz; Spiess, Philippe E; Bondaruk, Jolanta et al. (2012) Detection of bladder cancer using proteomic profiling of urine sediments. PLoS One 7:e42452|
|Diao, Lixia; Clarke, Charlotte H; Coombes, Kevin R et al. (2011) Reproducibility of SELDI Spectra Across Time and Laboratories. Cancer Inform 10:45-64|
|Chung, Woonbok; Bondaruk, Jolanta; Jelinek, Jaroslav et al. (2011) Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments. Cancer Epidemiol Biomarkers Prev 20:1483-91|
|Czerniak, Bogdan (2010) Molecular pathology and biomarkers of bladder cancer. Cancer Biomark 9:159-76|