دورية أكاديمية
Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy
| العنوان: | Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy |
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| المؤلفون: | Hartwig, Christina, Müller, Jan, Klett, Hagen, Kouhestani, Dina, Mittelstädt, Anke, Anthuber, Anna, David, Paul, Brunner, Maximilian, Jacobsen, Anne, Glanz, Karolina, Swierzy, Izabela, Roßdeutsch, Lotta, Klösch, Bettina, Grützmann, Robert, Wittenberger, Timo, Sohn, Kai, Weber, Georg F. |
| سنة النشر: | 2024 |
| المجموعة: | Publikationsdatenbank der Fraunhofer-Gesellschaft |
| مصطلحات موضوعية: | cfDNA, cfMBD-Seq, DMRs, Hybridization and capture, IPMN, Methylation, Next-generation sequencing, Non-invasive diagnostics, Pancreatitis, Pancreato-biliary cancer |
| الوصف: | Background: Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. Methods: Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing. Results: The hybridization and capture panel, covering around 74 kb in total, was applied to sequence a cohort of 25 PBCs, 25 pancreatitis patients, 25 clinical controls, and seven cases of Intraductal Papillary Mucinous Neoplasia (IPMN). An unbiased machine learning approach identified the 50 most discriminatory methylation markers for the discrimination of PBC from pancreatitis and controls resulting in an AUROC of 0.85 and 0.88 for a training (n = 45) and a validation (n = 37) data set, respectively. The panel was also able to distinguish high grade from low grade IPMN samples. Conclusions: We present a proof of concept for a methylation biomarker panel with better performance and improved discriminatory power than the current clinical marker CA19-9 for the discrimination of pancreato-biliary cancers from non-cancerous pancreatitis patients and clinical controls. This workflow might be used in future diagnostics for the detection of precancerous lesions, e.g. the identification of high grade IPMNs vs. low grade IPMNs. ; 23 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1476-4598 |
| العلاقة: | Molecular cancer; https://publica.fraunhofer.de/handle/publica/462491Test |
| DOI: | 10.1186/s12943-024-01943-x |
| الإتاحة: | https://doi.org/10.1186/s12943-024-01943-xTest https://publica.fraunhofer.de/handle/publica/462491Test |
| حقوق: | open access |
| رقم الانضمام: | edsbas.79A80C4A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14764598 |
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| DOI: | 10.1186/s12943-024-01943-x |