Biomarker identification may lead to new non-invasive test for colorectal cancer detection

June 13, 2013

A non-invasive test has been developed that measures methylation of the SDC2 gene in tissues and blood sera. It detected 87% of all stages of colorectal cancer (CRC) cases without a significant difference between early and advanced stages, while correctly identifying 95% of disease-free patients. The study is published in the July issue of The Journal of Molecular Diagnostics.

Searching for a biomarker that could be used for the early detection of CRC, investigators performed DNA microarray analysis coupled with enriched methylated DNA using tissues from primary tumors and non-tumor tissues from 12 CRC patients. After step-wise filtering, they found a set of genes that were highly methylated across all of the CRC tumors. Ultimately they identified SDC2, which encodes the membrane syndecan-2 protein, a protein that is known to participate in cell proliferation and cell migration and is expressed in colon mesenchymal cells. The methylation level of the target region of SDC2 assessed in tumor tissue was found to be significantly higher than that from paired adjacent non-tumor tissue.

The next step was to clinically validate the biomarker by analyzing SDC2 methylation levels in primary tumors and paired-adjacent non-tumor tissue samples from 133 CRC patients. Investigators found that in the transcriptional regulatory region of the SDC2 gene, tumor samples showed significantly higher levels of methylation than the control samples. SDC2 methylation positivity ranged from 92.9% to 100% when samples were stratified according to stages of cancer. Further, investigators found that the SDC2 biomarker could be measured in serum samples from CRC patients and healthy individuals. The authors suggest that the SDC2 methylation test could be used as a non-invasive alternative to or in conjunction with colonoscopy. Read the study abstract.

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