This renewal application, in response to the RFA CA-04-006 """"""""The Early Detection Research Network: Biomarker Developmental Laboratories"""""""" (EDRN/BDL), proposes an integrated multi-disciplinary biomarkers discovery and validation study centered at the University of Pittsburgh Cancer Institute (UPCI) focused on GI malignancies, specifically colon and pancreatic cancer. Two major Projects are proposed: (1) Nuclear Matrix Proteins for Early Detection of CRC, and (2) Luminex Multianalyte Profiling (LabMAP(r)) and SELDI-TOF-MS Serum Proteomic Profiling for Early Detection of Pancreatic Cancer. Both projects are firmly based on biomarker discoveries and strong preliminary data developed in our current EDRN/BDL grant and include a team of basic cancer researchers and clinicians supported by faculty with requisite expertise in biostatistics/bioinformatics. Project 1 will further characterize, evaluate, and validate a set of unique nuclear matrix proteins (NMPs) which are expressed in CRC. In preliminary data, the lead NMP biomarker, CC2, is elevated in the serum of CRC patients. A key objective of this Project is to undertake a more extensive Phase 1/2 validation study to assess the performance of this biomarker for serum-based early detection of CRC. Other NMPs in our development pipeline, with a varying spectrum of expression in pre-malignant (adenomas) and malignant tissue, will be further characterized and evaluated as potential biomarkers of early disease and/or risk. Project 2 will extend our preliminary data, developed with EDRN supplemental funds, obtained using two cutting-edge proteomic profiling technologies: 1) a unique panel of Luminex xMAP(r) multiplexed serologic biomarkers comprising multiple pancreatic cancer associated cytokines, chemokines, angiogenic and growth factors and their receptors, as well as circulating antibodies against pancreatic antigens; and 2) SELDI-TOF-MS, that both provide robust discrimination, in serum, of pancreatic cancer patients and case-matched controls. This Project will undertake an extensive Phase 1/2 validation study of these profiling technologies for pancreatic cancer early detection and clinical recurrence of disease. Lastly, as a parallel and focused biomarker discovery aim, we will determine the identity of the key diagnostic peptides/proteins that provide disease classification of the SELDI-TOF-MS profiles. These research Projects will be conducted in the context of an integrated UPCI EDRN/BDL, led by the continuing EDRN PI who brings extensive experience in cancer biomarkers and clinical proteomics research. This team is an outstanding and productive group of clinical and translational cancer researchers focused on cancer biomarkers discovery, evaluation, and validation. These efforts will strongly support the research and clinical goals of the EDRN.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA084968-10
Application #
7496624
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Wagner, Paul D
Project Start
1999-09-30
Project End
2011-06-30
Budget Start
2008-08-01
Budget End
2011-06-30
Support Year
10
Fiscal Year
2008
Total Cost
$599,404
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Wheeler, Sarah E; Morariu, Elena M; Bednash, Joseph S et al. (2012) Lyn kinase mediates cell motility and tumor growth in EGFRvIII-expressing head and neck cancer. Clin Cancer Res 18:2850-60
Wheeler, Sarah; Siwak, Doris R; Chai, Raymond et al. (2012) Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. Clin Cancer Res 18:2278-89
Bigbee, William L; Gopalakrishnan, Vanathi; Weissfeld, Joel L et al. (2012) A multiplexed serum biomarker immunoassay panel discriminates clinical lung cancer patients from high-risk individuals found to be cancer-free by CT screening. J Thorac Oncol 7:698-708
Zeng, Xuemei; Hood, Brian L; Sun, Mai et al. (2010) Lung cancer serum biomarker discovery using glycoprotein capture and liquid chromatography mass spectrometry. J Proteome Res 9:6440-9
Ostrow, Kimberly Laskie; Hoque, Mohammad O; Loyo, Myriam et al. (2010) Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. Clin Cancer Res 16:3463-72
Leman, Eddy S; Getzenberg, Robert H (2008) Nuclear structure as a source of cancer specific biomarkers. J Cell Biochem 104:1988-93
McLerran, Dale; Grizzle, William E; Feng, Ziding et al. (2008) Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias. Clin Chem 54:44-52
McLerran, Dale; Grizzle, William E; Feng, Ziding et al. (2008) SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer. Clin Chem 54:53-60
Leman, Eddy S; Schoen, Robert E; Magheli, Ahmed et al. (2008) Evaluation of colon cancer-specific antigen 2 as a potential serum marker for colorectal cancer. Clin Cancer Res 14:1349-54
Leman, Eddy S; Schoen, Robert E; Weissfeld, Joel L et al. (2007) Initial analyses of colon cancer-specific antigen (CCSA)-3 and CCSA-4 as colorectal cancer-associated serum markers. Cancer Res 67:5600-5

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