Evaluation of a Multi-Gene Methylation Blood-Test for the Detection of Colorectal Cancer

Abstract

Circulating tumour DNA biomarkers are an expanding field in oncology research that offer great potential but are currently often limited in value by overall cost. The aim of this study was to evaluate the efficacy of a novel multi-gene methylation blood test for the identification of colorectal cancer and throughout the spectrum of colorectal disease. Participants were recruited either prior to resection for known CRC or prior to screening colonoscopy after a positive faecal immunochemical test. Blood was collected from participants prior to their procedure being performed. The plasma was separated, and multiplex MethylLight droplet digital PCR was used to analyse for the presence of four methylated genes: SDC2, NPY, IKZF1 and SEPT9. A total of 537 participants underwent analysis. The SDC2/NPY genes showed a sensitivity of 33–54% and a specificity of 72–96%, whilst the IKZF1/SEPT9 genes showed a sensitivity of 19–42% and a specificity of 88–96%. Combining the two tests did not significantly increase the test accuracy. The sensitivity for advanced adenoma was 2–15%. There was a significant difference in the frequency of detectable methylation between the participants with CRC and those without CRC. However, neither the sensitivity nor the specificity was superior to current diagnostic screening tests.

Keywords

• circulating tumour DNA
• epigenetic methylation
• colorectal cancer
• cancer biomarkers