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

Sep 21, 2026

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The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is the low detection rate driven by limited biomarker abundance in plasma. Obstructive jaundice in PDAC allows routine bile collection, enabling liquid biopsy from both plasma and bile. The study assessed KRAS-mutated cftDNA detection by digital droplet PCR across healthy volunteers, PDAC, and other pancreatic neoplasms, comparing sensitivity and specificity across matrices.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Abstract

Introduction

Background and rationale

Liquid biopsy and KRAS relevance

biomedicines Article Cell-Free Tumor DNA Detection-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms Mark Jain 1, *, David Atayan 2, Tagir Rakhmatullin 3, Tatyana Dakhtler 2, Pavel Popov 2, Pavel Kim 2, Mikhail Viborniy 2, Iuliia Gontareva 2, Larisa Samokhodskaya 1 and Vyacheslav Egorov 2 Citation: Jain, M.; Atayan, D.; Rakhmatullin, T.; Dakhtler, T.; Popov, P.; Kim, P.; Viborniy, M.; Gontareva, I.; Samokhodskaya, L.; Egorov, V. Cell-Free Tumor DNA DetectionBased Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms. Biomedicines 2024, 12, 220. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/biomedicines12010220](10.3390/biomedicines12010220) Academic Editor: Konstantinos Dimas Received: 25 December 2023 Revised: 10 January 2024 Accepted: 16 January 2024 Published: 18 January 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Medical Research and Educational Center, Lomonosov Moscow State University, 119992 Moscow, Russia; [slm@fbm.msu.ru](slm@fbm.msu.ru) 2 Joint Stock Company “Ilyinsky Hospital”, 143421 Moscow, Russia; [d.atayan@ihospital.ru](d.atayan@ihospital.ru) (D.A.); [t.dakhtler@ihospital.ru](t.dakhtler@ihospital.ru) (T.D.); [p.popov@ihospital.ru](p.popov@ihospital.ru) (P.P.); [drpoul@yandex.ru](drpoul@yandex.ru) (P.K.); [m.vyborniy@ihospital.ru](m.vyborniy@ihospital.ru) (M.V.); [y.gontareva@ihospital.ru](y.gontareva@ihospital.ru) (I.G.); [v.egorov@ihospital.ru](v.egorov@ihospital.ru) (V.E.) 3 Department of Fundamental Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia; [tagir.rakhmatullin@internet.ru](tagir.rakhmatullin@internet.ru) * [Correspondence: jain-mark@outlook.com](Correspondence: jain-mark@outlook.com); Tel.: +7-916-574-46-84 Abstract: 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 KRAS-mutated cftDNA detection-based liquid biopsy of plasma and bile in patients with pancreatic neoplasms using digital droplet PCR. The study included healthy volunteers (n = 38), patients with PDAC (n = 95, of which 20 had obstructive jaundice) and other pancreatic neoplasms (OPN) (n = 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 (p < 0.01) . Plasma cftDNA levels were associated with distant metastases, tumor size, and CA 19-9 (p < 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; p = 0.005) but not in bile (p > 0.05) . Bile is a promising alternative to plasma in patients with obstructive jaundice, at least for the diagnostic purposes of liquid biopsy. Keywords: liquid biopsy; KRAS mutations; pancreatic ductal adenocarcinoma; pancreatic cancer; intraductal papillary mucinous neoplasm; digital droplet polymerase chain reaction; plasma; bile; prognosis; survival 1. Introduction Based on GLOBOCAN 2020 data, pancreatic cancer (PC) is ranked 14th in frequency and 7th in mortality amongst all oncological diseases [1] . It is estimated that by 2030, PC may be ranked significantly higher in terms of mortality,

FAQs

Why is cftDNA detection challenging in pancreatic ductal adenocarcinoma (PDAC)?

The study explains that plasma cftDNA detection is limited by the low overall abundance of this biomarker in plasma, leading to low detection rates.

What was the study’s aim and how was it tested?

To evaluate KRAS-mutated cftDNA detection-based liquid biopsy using plasma and bile, the study used digital droplet PCR across healthy volunteers and patient groups.

How do bile and plasma compare for cftDNA levels and detection?

Bile showed higher cftDNA levels than plasma and a higher detection rate, supporting bile as a promising alternative for patients with obstructive jaundice for diagnostic liquid biopsy.

Sep 21, 2026

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