The focus of this proposal is to continue development of a unique panel of colon cancer associated nuclear matrix proteins (NMPs), discovered and developed during our previous EDRN-sponsored, Biomarker Development Laboratory funding. NMPs offer the potential serum-based biomarkers for the early detection of colorectal cancer. This work has progressed substantially from testing of un-blinded single institution convenience samples all the way to testing of blinded, EDRN sponsored multi-institution reference sets. Markers were tested in different laboratory settings, cancer subtypes, and patient population characteristics. These data provide compelling potential for application in clinical populations. Currently two markers, CCSA-2 and CCSA-4 are poised for Phase ll-lll validation studies. We propose, with the help of established experts in assay development, to further refine those assays to position them for definitive clinical testing. In addition, we will advance NMP markers related to liver metastasis. The two major objectives 1. To OPTIMIZE AND REFINE the CCSA-2 and CCSA-4 assays and test them in a series of small scale experiments to position them for definitive evaluation within the EDRN mechanism. In specific, we aim to (a) develop robust assays for the accurate and precise measurement of CCSA-2 and CCSA-4;(b) test the assays under a variety of clinical circumstances and conditions to understand, and anticipate sources of error and potential problems in implementation that might be encountered when testing the assays on a larger scale. The goal of this first objective is to deliver two assays to validation with ample preliminary testing to maximize the potential for success in the EDRN program. 2. To develop NMP markers for liver metastasis. We have identified proteins in liver metastasis tissue specimens that are neither present in adjacent uninvolved liver nor in liver from normal donors. These proteins are prime candidates for assay development for markers of advanced disease. We propose (a) to isolate, characterize and develop antibodies for serum detection of liver metastasis proteins, (b) to evaluate these antibodies in appropriate clinical specimens for eventual delivery for EDRN validation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA152753-03
Application #
8287646
Study Section
Special Emphasis Panel (ZCA1-SRLB-C (M1))
Program Officer
Wagner, Paul D
Project Start
2010-09-07
Project End
2015-06-30
Budget Start
2012-08-17
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$632,461
Indirect Cost
$192,642
Name
Johns Hopkins University
Department
Urology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Robles, Ana I; Traverso, Giovanni; Zhang, Ming et al. (2016) Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers. Gastroenterology 150:931-43
Negm, Ola H; Hamed, Mohamed R; Schoen, Robert E et al. (2016) Human Blood Autoantibodies in the Detection of Colorectal Cancer. PLoS One 11:e0156971
Schoen, Robert E; Razzak, Anthony; Yu, Kelly J et al. (2015) Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer. Gastroenterology 149:1438-1445.e1
Ho, Gloria Y F; Jung, Hwa J; Schoen, Robert E et al. (2015) Differential expression of circulating microRNAs according to severity of colorectal neoplasia. Transl Res 166:225-32
Wang, Yuxuan; Springer, Simeon; Mulvey, Carolyn L et al. (2015) Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med 7:293ra104
Tie, J; Kinde, I; Wang, Y et al. (2015) Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol 26:1715-22
Schoen, Robert E; Machicado, Jorge D (2015) Detection of Advanced Neoplasia with FIT Versus Flexible Sigmoidoscopy Versus Colonoscopy: More Is More. Dig Dis Sci 60:1123-5
Bettegowda, Chetan; Sausen, Mark; Leary, Rebecca J et al. (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24
Mooney, Steven M; Rajagopalan, Krithika; Williams, Brenten H et al. (2011) Creatine kinase brain overexpression protects colorectal cells from various metabolic and non-metabolic stresses. J Cell Biochem 112:1066-75