Liquid biopsy, using a novel DNA methylation signature, distinguishes pancreatic adenocarcinoma from benign pancreatic disease

Abstract

We tested the ability of a novel DNA methylation biomarker set to distinguish metastatic pancreatic cancer cases from benign pancreatic cyst patients and to monitor tumor dynamics using quantitative DNA methylation analysis of cell-free DNA (cfDNA) from blood samples. The biomarkers were able to distinguish malignant cases from benign disease with high sensitivity and specificity (AUC = 0.999). Furthermore, the biomarkers detected a consistent decline in tumor-derived cfDNA in samples from patients undergoing chemotherapy. The study indicates that our liquid biopsy assay could be useful for management of pancreatic cancer patients.

Noninvasive detection of pancreatic ductal adenocarcinoma using the methylation signature of circulating tumour DNA

“…In addition to diagnostic, monitoring and prognostic applications [ 44 , 45 ], ctDNA methylation has been investigated in recent years as a possible early detection biomarker in PDAC [ 17 , 46 – 49 ]. Most of these studies were based on relatively small sample sizes and evaluated individual differentially methylated CpG sites or genes, which were typically selected from literature searches or by in silico prediction and might not be able to capture the complex biology of PDAC.…”

Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment

“…The concurrent analyses of hundreds of methylation marks in cfDNA also allowed for the differentiation among various gastrointestinal cancers, including PDAC [ 89 ]. In a recent study, a set of 10 cfDNA methylation markers ( MIR129-2 , LINC01158 , CCDC181 , PRKCB , TBR1 , ZNF781 , MARCH11 , VWC2 , SLC9A3 , HOXA7 ) demonstrated a very good performance with 100% sensitivity at 95% specificity to distinguish between metastatic pancreatic cancer and benign pancreatic cysts [ 91 ].…”

“…The importance of analyzing cfDNA methylation cannot only be limited to PDAC diagnosis, it may become of clinical significance for prognostication of the disease and treatment monitoring [ 91 , 97 , 98 , 99 , 100 ].…”

“…Owing to its non-invasive nature, plasma cfDNA allows serial monitoring of tumor burden and evolution under treatment, which cannot be realized by tissue biopsy [ 101 ]. Although data on cfDNA methylation under treatment are scarce, a decrease in cfDNA methylation levels has been reported in patients undergoing chemotherapy [ 91 ].…”

“…Liquid biopsy is emerging as a reliable and non-invasive biomarker approach for diagnosis, prognostication and/or treatment monitoring in PDAC. cfDNA methylation patterns are able to differentiate between PDAC and benign pancreatic conditions with already relatively high accuracy [ 81 , 82 , 83 , 84 , 85 , 86 , 90 , 91 , 92 , 94 , 95 , 96 ]. Moreover, cfDNA methylation markers have demonstrated promising results for identifying metastatic stage and estimating the prognosis of PDAC patients [ 84 , 97 , 98 , 99 , 100 ].…”