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Article

Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer

1
Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany
2
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany
3
Department of General, Thoracic and Pediatric Surgery, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2021, 13(1), 39; https://doi.org/10.3390/cancers13010039
Received: 23 November 2020 / Revised: 16 December 2020 / Accepted: 22 December 2020 / Published: 25 December 2020
To elucidate and compare the value of plasma and bile as liquid biopsy source, cfDNA from 80 patients with pancreatobiliary cancers or non-malignant biliary obstructions was subjected to panel-based next generation sequencing (NGS). Results showed high correspondence in mutational profiles of bile-derived cfDNA and matched tissue samples, and the method proved superior to traditional plasma-based liquid biopsy techniques and with higher sensitivity than routine biomarkers such as CA19-9.
Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma. Blood (n = 37) and bile (n = 21) samples were collected from patients affected by pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (CCA) or with non-malignant biliary obstructions (blood n = 16; bile n = 21). Panel-based next generation sequencing (NGS) and digital droplet PCR (ddPCR) were applied for tumor mutation profiling. NGS results from matched tumor tissues (n = 29) served as comparison. Sequencing of cfDNA from bile resulted in detection of 96.2% of the pathogenic tumor mutations found in matched tissue samples. On the other hand, only 31.6% of pathogenic tumor mutations found in tissue could be detected in plasma. In a direct comparison, only half of the mutations detected in bile cfDNA were concordantly detected in plasma from the same patients. Panel NGS and ddPCR displayed comparable sensitivity. In conclusion, bile is a suitable source of cfDNA for the diagnosis of pancreatobiliary cancer and performs more reliably than plasma. Although primary diagnosis still requires histologic confirmation, bile-derived cfDNA could offer an alternative if tissue sampling is not feasible and might allow less invasive disease monitoring. View Full-Text
Keywords: pancreatic cancer; cholangiocarcinoma; cell-free DNA; liquid biopsy; ERCP; next generation sequencing pancreatic cancer; cholangiocarcinoma; cell-free DNA; liquid biopsy; ERCP; next generation sequencing
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MDPI and ACS Style

Driescher, C.; Fuchs, K.; Haeberle, L.; Goering, W.; Frohn, L.; Opitz, F.V.; Haeussinger, D.; Knoefel, W.T.; Keitel, V.; Esposito, I. Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer. Cancers 2021, 13, 39. https://doi.org/10.3390/cancers13010039

AMA Style

Driescher C, Fuchs K, Haeberle L, Goering W, Frohn L, Opitz FV, Haeussinger D, Knoefel WT, Keitel V, Esposito I. Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer. Cancers. 2021; 13(1):39. https://doi.org/10.3390/cancers13010039

Chicago/Turabian Style

Driescher, Caroline, Katharina Fuchs, Lena Haeberle, Wolfgang Goering, Lisa Frohn, Friederike V. Opitz, Dieter Haeussinger, Wolfram T. Knoefel, Verena Keitel, and Irene Esposito. 2021. "Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer" Cancers 13, no. 1: 39. https://doi.org/10.3390/cancers13010039

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