Abstract
396
Colorectal cancer (CRC) is a major cause of cancer death in both men and women. It is estimated that there will be 104,950 new cases and 56,290 deaths in the US in 2005, accounting for a large proportion of all cancer deaths. It is recognized that CRC is curable by resection when localized. We have focused our efforts to develop CRC serum and tissue biomarkers, and a non-invasive serum-based immunoassay for the detection of early stage I/II localized resectable CRC. We have applied our proprietary technologies to discover and validate a panel of biomarkers using a multiplex screening platform known as Matrix Protein Array Technology (MPAT). The MPAT involves the screening of clinical samples with a large collection of 70,000 distinct polyclonal antibodies. Total proteome from normal and cancer tissue or serum samples were printed on a solid support, then allowed to interact with individual antibodies, and the reaction was detected by chemiluminescence. Computer analysis of a CCD-acquired image quantified each spot. Statistical analysis of the data points enabled the selection of a panel of tissue and serum biomarkers that are differentially and specifically expressed in early stage CRC. We have examined the CRC specific biomarkers in over 654 human tissue biopsy specimens, and in over 1083 human serum specimens. In both cases, samples were from localized adenocarcinoma (stage I/II) CRC patients, normal and benign controls, as well as from other cancers and inflammatory disorders of the gastrointestinal tract. The sensitivity and specificity of each biomarker varied from 65% to 95%, and sensitivity of tissue biomarkers was markedly higher than that of independently identified serum biomarkers. We are fully characterizing serum biomarkers, producing a large supply of monospecific antibodies, and setting up a serum-based diagnostic immunoassay for the early detection of localized resectable CRC. The current FOBT screening methodology recommended for early detection of CRC, while associated to decreased CRC mortality, is not highly sensitive. Our data support the utility application of this immunoassay as a population screening method for CRC early detection. Tissue biomarkers, whether alone or in combination with the serum biomarkers, may be used as cancer diagnostic imaging agents, as well as for CRC prognosis and therapy response.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]