Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/1/39 |
| _version_ | 1797543604346945536 |
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| author | Caroline Driescher Katharina Fuchs Lena Haeberle Wolfgang Goering Lisa Frohn Friederike V. Opitz Dieter Haeussinger Wolfram Trudo Knoefel Verena Keitel Irene Esposito |
| author_facet | Caroline Driescher Katharina Fuchs Lena Haeberle Wolfgang Goering Lisa Frohn Friederike V. Opitz Dieter Haeussinger Wolfram Trudo Knoefel Verena Keitel Irene Esposito |
| author_sort | Caroline Driescher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:47:01Z |
| format | Article |
| id | doaj.art-faee83ed26ba4aa194bebbb77a6f5539 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:47:01Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-faee83ed26ba4aa194bebbb77a6f55392023-11-21T02:31:46ZengMDPI AGCancers2072-66942020-12-011313910.3390/cancers13010039Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary CancerCaroline Driescher0Katharina Fuchs1Lena Haeberle2Wolfgang Goering3Lisa Frohn4Friederike V. Opitz5Dieter Haeussinger6Wolfram Trudo Knoefel7Verena Keitel8Irene Esposito9Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of General, Thoracic and Pediatric Surgery, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, GermanyCurrently 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.https://www.mdpi.com/2072-6694/13/1/39pancreatic cancercholangiocarcinomacell-free DNAliquid biopsyERCPnext generation sequencing |
| spellingShingle | Caroline Driescher Katharina Fuchs Lena Haeberle Wolfgang Goering Lisa Frohn Friederike V. Opitz Dieter Haeussinger Wolfram Trudo Knoefel Verena Keitel Irene Esposito Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer Cancers pancreatic cancer cholangiocarcinoma cell-free DNA liquid biopsy ERCP next generation sequencing |
| title | Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer |
| title_full | Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer |
| title_fullStr | Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer |
| title_full_unstemmed | Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer |
| title_short | Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer |
| title_sort | bile based cell free dna analysis is a reliable diagnostic tool in pancreatobiliary cancer |
| topic | pancreatic cancer cholangiocarcinoma cell-free DNA liquid biopsy ERCP next generation sequencing |
| url | https://www.mdpi.com/2072-6694/13/1/39 |
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