Tumor cell-free DNA detection-based liquid biopsy of plasma and bile in pancreatic ductal adenocarcinoma: a pilot study

Author:

Jain MarkORCID,Atayan David P.ORCID,Rakhmatullin Tagir I.ORCID,Dakhtler Tatyana E.ORCID,Popov Pavel A.ORCID,Kim Pavel P.ORCID,Gontareva Julia V.ORCID,Samokhodskaya Larisa M.ORCID,Egorov Vyacheslav I.ORCID,Kamalov Armais A.ORCID

Abstract

INTRODUCTION: Plasma liquid biopsy with tumor cell-free DNA detection is one of the most promising technologies in pancreatic ductal adenocarcinoma diagnosis. Due to low levels of this biomarker in plasma its detectability turns out to be lower than expected. However, some patients with this disease present with biliary obstruction, which enables collection of bile for tumor cell-free DNA analysis. THE AIM: To comparison of diagnostic potential of cell-free tumor DNA detection-based liquid biopsy of plasma and bile in pancreatic ductal adenocarcinoma patients. MATERIAL AND METHODS: The pilot study included 15 primary untreated pancreatic ductal adenocarcinoma patients with biliary obstruction. Cell-free DNA was isolated from 5 mL of plasma and 5 mL of bile. Tumor cell-free DNA detection was performed using digital droplet PCR with KRAS gene mutations analysis: G12A, G12C, G12D, G12R, G12S, G12V, G13D и Q61H (183AC), Q61H (183AT), Q61K, Q61L, Q61R. False-positive droplets threshold was established during the analysis of plasma cell-free DNA samples from 15 healthy volunteers. RESULTS: Tumor cell-free DNA was detected in 13 out of 15 bile samples, whereas among paired plasma samples only 9 were positive. All plasma positive samples had a paired positive bile sample. Tumor cell-free DNA levels were statistically significantly higher in bile than in plasma: 538.0 (4.11960.0) vs. 4.4 (027.6) copies/mL (p=0.005). CONCLUSION: Bile liquid biopsy in pancreatic ductal adenocarcinoma patients with biliary obstruction is a promising alternative to plasma analysis, due to higher concentrations of tumor cell-free DNA.

Publisher

ECO-Vector LLC

Subject

Transplantation,Cell Biology,Molecular Biology,Biomedical Engineering,Surgery,Biotechnology

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