The goal of this proposal is to develop serologic tests for early detection of colorectal neoplasia and colon cancer. Colorectal cancer is the second leading cause of cancer death. Early detection of colorectal adenomas and of early stage colon cancers can be life saving, but no sensitive and specific non-invasive test for such screening currently exists. My laboratory has discovered two novel genes, Colon Cancer Secreted Protein-1 (CCSP-1) and Colon Cancer Secreted Protein-2 (CCSP-2), that we have shown are expressed in colon adenomas and cancers, but not in normal colon or other normal tissues and that encode secreted proteins. We have further shown that we can detect epitope tagged CCSP-1 and CCSP-2 proteins secreted into the circulation of mice bearing colon cancer xenografts that express these tagged proteins.
The specific aims of this project are to: 1. Establish an immunoassay for detection of CCSP-1 and CCSP-2 proteins in human serum. 2. Determine the individual and joint sensitivity and specificity of CCSP-1 and CCSP-2 proteins for serologic detection of individuals having early and late stage colon cancers versus individuals having normal colonoscopic exams, as well as versus additional control cohorts of individuals having hyperplastic polyps, individuals having inflammatory bowel disease, and individuals having other non-colonic malignancies. 3. Determine the individual and joint sensitivity and specificity of CCSP-1 and CCSP-2 proteins for serologic detection of advanced colon adenomas. This research is directly relevant to the improvement of public health. Over 50,000 Americans will die of colorectal cancer this year, and all these deaths are in principle preventable by effective screening able to detect colon cancer during its early stages, when these cancers are fully amenable to surgical cure. Development of a simple screening blood test for detecting this disease would overcome the current barriers of cost and public acceptability that have so far limited the availability and acceptability of colonoscopic screening to only a minority of the at risk population of adults age 50 and older, for all of whom colon cancer screening has been recommended. ? ? ?
| Dazard, Jean-Eudes; Rao, J Sunil; Markowitz, Sanford (2012) Local sparse bump hunting reveals molecular heterogeneity of colon tumors. Stat Med 31:1203-20 |
| Li, Meng; Chen, Wei-Dong; Papadopoulos, Nickolas et al. (2009) Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol 27:858-63 |
| Guo, Chunguang; Zhang, Xiaodong; Fink, Stephen P et al. (2008) Ugene, a newly identified protein that is commonly overexpressed in cancer and binds uracil DNA glycosylase. Cancer Res 68:6118-26 |
| Jones, Sian; Chen, Wei-Dong; Parmigiani, Giovanni et al. (2008) Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci U S A 105:4283-8 |
