Blood-based DNA test effectively detects colorectal cancer

Researchers have identified a biomarker for colorectal cancer that can be obtained from a small amount of serum DNA in less than 1 mL of blood and that is highly sensitive and specific for the disease, particularly in the early stages.

Aberrant DNA methylation has shown promise as a biomarker for the early detection of cancer, wrote TaeJeong Oh, PhD, of Genomictree, Inc., a molecular diagnostics company in Daejeon, South Korea, and colleagues in The Journal of Molecular Diagnostics. (Investigators from Yonsei University College of Medicine in Seoul, South Korea, were also involved in the study.)

To explore further the potential of DNA methylation as a biomarker for colorectal cancer, Oh's team performed DNA microarray analysis coupled with enriched methylated DNA, using tissues from primary tumors as well as nontumor tissues in 12 persons with colorectal cancer (stage I, II, III, or IV). This work uncovered a set of genes that were highly methylated across all of the tumors, as explained in a statement from the journal publisher.

Additional study led to the identification of one particular gene, SDC2, which encodes the membrane syndecan-2 protein. This protein is known to participate in cell proliferation and cell migration, and is expressed in colon mesenchymal cells.

After finding that the methylation level of target region of SDC2 assessed in tumor tissue was significantly higher than that from paired-adjacent nontumor tissue, Oh's group sought to clinically validate the biomarker. This was accomplished by analyzing SDC2 methylation levels in primary tumors and in paired-adjacent nontumor tissue samples from approximately 130 persons with colorectal cancer.

This analysis revealed a much higher level of aberrant SDC2 methylation in most primary tumors (97.8%) compared with corresponding nontumor tissue in persons with colorectal cancer, irrespective of clinical stage. SDC2 methylation positivity ranged from 92.9% to 100% when samples were stratified by cancer stage.

The investigators also found that the biomarker could be measured in serum samples from persons with colorectal cancer and from healthy persons, using less than 1 mL of blood. However, advised Genomictree CEO and study coauthor Dr. Sungwhan An in the statement, “I believe a greater volume of blood will further improve the clinical performance of the test.”

Clinical validation of the test in serum DNA from 131 persons with colorectal cancer at stages I to IV and from 125 healthy individuals demonstrated a high sensitivity of 87% in detecting cancers, with a specificity of 95.2%. Sensitivity at stage I, when therapeutic interventions have the greatest likelihood of cure, was 92.3%, indicating the potential of SDC2 methylation as a blood-based DNA test for early detection of colorectal cancer.
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