Abstract 4517: Syndecan-2 methylation is an early detection biomarker for colorectal cancer with high sensitivity and specificity in small serum sample volumes

BACKGROUND: Colorectal cancer (CRC) is a major cause of morbidity and mortality in the world. Epigenetics has been a useful tool in the development of sensitive and specific screening tests for CRC. Targeting genes highly methylated in CRC has allowed us to develop an accurate method to select novel candidate genes and validate their sensitivity and selectivity through testing in clinical samples. METHODS: We performed CpG microarray analysis using methylation enriched DNA from tumors and matched normal appearing tissues to identify genes methylated in CRC. We then applied a step-wise filtering method to narrow our field of candidate genes. Six genes were verified for high methylation-positivity in CRC cell lines and underwent negative selection in healthy normal samples using bisulfate-pyrosequencing. Genes SORCS3, SIM1, SDC2 were selected for low levels of methylation in normal tissue followed by verification with MSP-pyrosequencing. RESULTS: SDC2 was then selected because of high methylation levels in tumor and very low levels in normal tissue. SDC2 methylation levels were measured in 133 tumors and were found to be significantly methylated at all stages. Next, 500αl sera samples from 42 CRC patients were tested using qMSP which demonstrated sensitivity at 71.4% and specificity 92.9%. CONCLUSIONS: This study utilized refined technologies to identify and validate a novel candidate SCD2 for CRC screening in serum with high sensitivity and selectivity using only 500αl. These findings demonstrate a new level of candidate selection, verification and application that we feel will meet the need for a new minimally-invasive screening test. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4517. doi:1538-7445.AM2012-4517