Cell-Free Tumor DNA Detection-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms

The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is overcoming its low detection rate, which is mainly explained by the overall scarcity of this biomarker in plasma. Obstructive jaundice is a frequent event in PDAC, which enables bile collection a...

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Published in:Biomedicines 2024-01, Vol.12 (1), p.220
Main Authors: Jain, Mark, Atayan, David, Rakhmatullin, Tagir, Dakhtler, Tatyana, Popov, Pavel, Kim, Pavel, Viborniy, Mikhail, Gontareva, Iuliia, Samokhodskaya, Larisa, Egorov, Vyacheslav
Format: Article
Language:English
Subjects:
Adenocarcinoma
Bile
Biopsy
Cancer
digital droplet polymerase chain reaction
Disease
DNA
Ethylenediaminetetraacetic acid
Genetic aspects
Genetic testing
intraductal papillary mucinous neoplasm
Jaundice
KRAS mutations
Laboratories
liquid biopsy
Metastases
Metastasis
Mortality
Mutation
Pancreas
Pancreatic cancer
pancreatic ductal adenocarcinoma
Performance evaluation
Plasma
Survival analysis
Tomography
Tumors
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Summary:The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is overcoming its low detection rate, which is mainly explained by the overall scarcity of this biomarker in plasma. Obstructive jaundice is a frequent event in PDAC, which enables bile collection as a part of routine treatment. The aim of this study was to evaluate the performance of -mutated cftDNA detection-based liquid biopsy of plasma and bile in patients with pancreatic neoplasms using digital droplet PCR. The study included healthy volunteers ( = 38), patients with PDAC ( = 95, of which 20 had obstructive jaundice) and other pancreatic neoplasms (OPN) ( = 18). The sensitivity and specificity compared to the control group were 61% and 100% (AUC-ROC-0.805), and compared to the OPN group, they were 61% and 94% (AUC-ROC-0.794), respectively. Bile exhibited higher cftDNA levels than plasma (248.6 [6.743; 1068] vs. 3.26 [0; 19.225] copies/mL) and a two-fold higher detection rate ( < 0.01). Plasma cftDNA levels were associated with distant metastases, tumor size, and CA 19-9 ( < 0.05). The probability of survival was worse in patients with higher levels of cftDNA in plasma (hazard ratio-2.4; 95% CI: 1.3-4.6; = 0.005) but not in bile ( > 0.05). Bile is a promising alternative to plasma in patients with obstructive jaundice, at least for the diagnostic purposes of liquid biopsy.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12010220