Preliminary Validation of Biomarkers for the Detection of Colorectal Adenomas (Team Project #1)
- Abbreviated Name
- Colon Team Project #1
- Lead Investigator
- — University of Michigan
- Coordinating Investigator
- — University of Michigan
- Involved Investigators
-
- — University of Michigan
- Markowitz, Sanford — Case Western Reserve University
- Lampe, Paul — Fred Hutchinson Cancer Center
- Schoen, Robert E. — University of Pittsburgh Cancer Institute
- Grady UW, William — University of Washington
- Hanash, Samir — The University of Texas MD Anderson Cancer Center
- Srivastava, Sudhir — National Cancer Institute
- Getzenberg, Robert — Johns Hopkins University
Abstact
No abstract availalbe.
Aims
We propose a GI Collaborative biomarker validation project with the goal of identifying those biomarkers developed by the GI collaborative that will predict the presence of advanced colorectal adenomas. Biomarkers from the diverse colon focused and pancreatic focused BDLs of the GI Collaborative will assay their biomarkers on sets of identical reference set samples. The GI Collaborative will also assess markers of tissue/serum-plasma and/or urine from other EDRN collaborative groups, i.e. urologic, breast, lung, in this reference set. The most promising biomarkers that meet required adenoma detection bars will be assayed in a second, blinded test set of biosamples from a separate group of subjects before being considered for inclusion in large, cross sectional biomarker validation project for the early detection of both colorectal adenocarcinomas and advanced adenomas. Aim 1 To define preliminary sensitivity, specificity, and their variance of biomarkers for the detection of advanced adenomas in a standardized, open labeled training biosample reference set. Aim 2 To select those biomarkers for the detection of advanced adenomas in the training set for additional validation in a standardized biosample reference test set using pre-set performance characteristics. Aim 3 To verify sensitivity, specificity, and their variance of biomarkers for the detection of advanced adenomas in a standardized, blinded test biosample reference set. Aim 4 To select biomarkers for the detection of advanced adenomas from the test set for inclusion in a large, cross sectional validation trial of biomarkers for the early detection of advanced adenomas.
Analytic Method
Markowitz Approach: Candidate aberrant methylated loci will be identified from RRBS analysis of tissues in the archive of the Case Medical Center. Real-time MS-PCR assays will be developed to quantitatively assay for these aberrant methylation events. Validation of these methylation events, their timing, and their selectivity for neoplasia, will be examined in tissue samples from the GLNE archive including normal mucosal biopsy from individuals with clean colonoscopies, normal mucosal biopsies from individuals with colon neoplasia (advanced adenomas or cancers), biopsies of non-advanced adenomas, biopsies of advanced adenomas, biopsies of early stage colon cancers, and biopsies of late stage colon cancers. Marker loci that show sensitivity and specificity for colon neoplasia at the independent tissue collections of the GLNE will be tested for their sensitivity and specificity for early and late neoplasia detection in body fluids including in fecal DNAs and in plasma samples. Grady Approach: Quantitative CpG methylation assessment with quantitative methylation specific PCR (qMSP or MethyLight). Lampe compare protein expression/activation in adenoma vs. normal colon mucosa via antibody array to discover diagnostic/prognostic biomarkers. The best diagnostic and prognostic markers will then be rescreened on a tissue microarrays. After triage, we will determine whether the surviving biomarkers are adenoma or stromal derived by analyzing its expression pattern. Getzenberg evaluate the potential of CKB IHC staining within the colon to serve as a marker for the development of colon cancer and perhaps at the onset of adenomas. The laboratory is now developing a sandwich ELISA to detect CCSA-2 in the serum and would propose to evaluate this marker
Publications
- No publications available at this time for this protocol.
Biomarkers
Data Collections
- No data collections available at this time for this protocol.
Team Project
- Start Date
- Sep 1 2011
- Estimated Finish Date
- Sep 1 2014
- Finish Date
- Sep 1 2014
- Protocol ID
- 347
- Protocol Type
- Collaboration
- Field of Research
- Genomics
- Collaborative Group
- G.I. and Other Associated Cancers Research Group
- Cancer Types
-
- Malignant neoplasm of colon
- Phased Status
- 1