Using Epigenetics to Identify Colorectal Cancer in Blood-Based Samples
Posted: Wednesday, January 22, 2020
A recent Danish study published in Clinical Epigenetics used a minimally invasive blood-based assay called TriMeth to detect early-stage colorectal cancer. Sarah Østrup Jensen, PhD, and colleagues used droplet digital polymerase chain reaction (PCR) to reveal novel DNA methylation patterns in the genes C9orf50, KCNQ5, and CLIP4 in patients with colorectal cancer.
“TriMeth enables detection of early-stage colorectal cancer with high sensitivity and specificity,” the investigators concluded. “The reported results underline the potential utility of DNA methylation-based detection of circulating tumor DNA in the clinical management of colorectal cancer.”
Phase I of the study focused on the discovery of DNA methylation markers in colorectal cancer. Through this phase, researchers used data from previously acquired and publicly available HumanMethlation450K BeadChip arrays from numerous colorectal tumors and other cancer types. They used a stepwise strategy to reveal 29 DNA methylation sites that were colorectal-specific. The 29 targets were then clinically assayed between 30 patients with colorectal tumors and 30 healthy individuals. This process identified methylation of C9orf50, KCNQ5, and CLIP4 in 70% of patients with colorectal tumors and none in the control patients.
In phase II, the research group developed TriMeth to detect early colorectal cancer from plasma samples. Preoperative plasma was acquired from 256 patients diagnosed with stage I to IV colorectal cancer at Aarhus University Hospital, whereas control plasma was acquired from 178 participants without colorectal cancer. Using methylation-specific droplet digital PCR, the researchers screened for C9orf50, KCNQ5, and CLIP4 in colorectal and control plasma samples. Using receiver operating characteristics curves, the authors effectively discriminated patients with colorectal cancer from controls, with 76% sensitivity for C9orf50; 83%, for KCNQ5; and 77%, for CLIP4. Finally, using a two-of-three scoring algorithm, TriMeth was applied to an independent validation cohort, which successfully identified patients with colorectal cancer at a sensitivity of 91% overall.
Disclosure: The study authors reported no conflicts of interest.