Bladder cancer (BCa) is among the five most common malignancies worldwide. In the US alone, new BCa cases for 2012 are estimated at 73,500 with estimated deaths at 14,880. At presentation, the majority of bladder tumors are non?muscle invasive, and can be treated by transurethral resection of the tumor, however, more than 70% of patients with BCa will have a recurrence during the first two years after diagnosis. This recurrence phenomenon makes BCa one of the most prevalent cancers worldwide. Furthermore, once treated, patients are under continued surveillance with routine cystoscopy for detection of new tumor development, so the healthcare costs of BCa are a major burden. The overall goal of this project is to develop assays that can achieve the accurate, non?invasive detection of BCa via urinalysis. Using high?throughput genomic profiling technologies, we have derived a series of molecular signatures that outperform any currently used urinalysis assay for BCa detection. The first specific aims are designed to validate the diagnostic accuracy of components of these signatures using alternative techniques. The goal is to establish the technical and scientific merit of the approach. Further specific aims will be designed to determine the feasibility of developing selected nucleic acid?based molecular signatures into robust assays with clinical utility. At the end of the proposed study, assays will be ready for development for use in the clinic. The development of non?invasive, urine based assays for bladder cancer detection and disease status evaluation will be of tremendous benefit to both patients and the healthcare system.

Public Health Relevance

Bladder cancer is one of the most prevalent cancers in the world, due partly to its persistent recurrence after initial treatment. The development of accurate assays that can detect and monitor bladder cancer non-invasively through urine analysis would be a major advance over current modalities and would benefit both patients and healthcare systems. The goal of this project is to develop diagnostic assays for bladder cancer that can be commercialized for clinical utility.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA116161-08
Application #
9224988
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Mckee, Tawnya C
Project Start
2007-09-01
Project End
2020-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
8
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Mayo Clinic Jacksonville
Department
Type
DUNS #
153223151
City
Jacksonville
State
FL
Country
United States
Zip Code
32224
Sankpal, Umesh T; Goodison, Steve; Jones-Pauley, Michelle et al. (2017) Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells. Oncotarget 8:14593-14603
Urquidi, Virginia; Netherton, Mandy; Gomes-Giacoia, Evan et al. (2016) A microRNA biomarker panel for the non-invasive detection of bladder cancer. Oncotarget 7:86290-86299
Huang, Sijia; Kou, Lei; Furuya, Hideki et al. (2016) A Nomogram Derived by Combination of Demographic and Biomarker Data Improves the Noninvasive Evaluation of Patients at Risk for Bladder Cancer. Cancer Epidemiol Biomarkers Prev 25:1361-6
Urquidi, Virginia; Netherton, Mandy; Gomes-Giacoia, Evan et al. (2016) Urinary mRNA biomarker panel for the detection of urothelial carcinoma. Oncotarget 7:38731-38740
Miyake, M; Goodison, S; Lawton, A et al. (2015) Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway. Oncogene 34:890-901
Miyake, Makito; Lawton, Adrienne; Dai, Yunfeng et al. (2014) Clinical implications in the shift of syndecan-1 expression from the cell membrane to the cytoplasm in bladder cancer. BMC Cancer 14:86
Zhang, Ge; Miyake, Makito; Lawton, Adrienne et al. (2014) Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors. BMC Cancer 14:310
Chen, Li-Mei; Chang, Myron; Dai, Yunfeng et al. (2014) External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort. Cancer Epidemiol Biomarkers Prev 23:1804-12
Zhang, Ge; Gomes-Giacoia, Evan; Dai, Yunfeng et al. (2014) Validation and clinicopathologic associations of a urine-based bladder cancer biomarker signature. Diagn Pathol 9:200
Giacoia, Evan Gomes; Miyake, Makito; Lawton, Adrienne et al. (2014) PAI-1 leads to G1-phase cell-cycle progression through cyclin D3/cdk4/6 upregulation. Mol Cancer Res 12:322-34

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