Development and clinical validation of a blood test based on 29-gene expression for early detection of colorectal cancer

A blood test for colorectal cancer (CRC) screening is a valuable tool to for testing asymptomatic individuals and reducing CRC-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with CRC and adenomatous polyps (AP) from individuals with a negative colonoscopy. Experimental Design: A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) {greater than or equal to}1cm, 45 CRC, and independently validated on 74 controls, 42 LAP, 52 CRC (23 Stages I-II) as well as on 245 cases including other colorectal findings and diseases other than CRC. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers. Results: The 29-gene algorithm detected CRC and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers CEA and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for CRC and LAP detection of 78.1% and 52.3%, respectively. Conclusions: We report the validation of a novel blood test, Colox®, for the detection of CRC and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provides physicians a useful tool to test average risk individuals unwilling to undergo upfront colonoscopy.