Abstract
Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.
Highlights
Liquid biopsies are noninvasive tests that detect fragments of DNA or cells circulating in the blood
For the DNA methylation markers selected based on the criteria described above, we designed MethyLight primers and probes for eight methylated markers (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B)
To examine whether these eight DNA methylation markers were comparable to the Laird team’s DNA-methylation markers THBD and c9orf50 for the detection of colorectal cancer (CRC) with plasma cell-free DNA (cfDNA) samples, we analyzed the performance of these ten methylation markers
Summary
Liquid biopsies are noninvasive tests that detect fragments of DNA or cells circulating in the blood. Blood samples can be collected without a significant risk of causing harm when trying to reach affected organs that are difficult to access. Comes from healthy, inflamed, or cancerous tissue as a result of apoptosis or necrosis. These DNA segments are approximately 170 bp in length on average and have a halflife of approximately 2 h [1,2]. Circulating tumor DNA (ctDNA) refers to tumor cellderived cfDNA and comprises a minor portion of cfDNA in the blood [3]. Liquid biopsy studies utilize properties of ctDNA, including tumor-specific mutations or copy number
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
