2025-08-01 フラウンホーファー研究機構(Fraunhofer)
© Piotr Banczerowski Model of cell-free tumor DNA used for differential methylation analyses
<関連情報>
- https://www.fraunhofer.de/en/press/research-news/2025/august-2025/early-pancreatic-cancer-detection.html
- https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01943-x
- https://www.mdpi.com/2072-6694/15/7/1924
非侵襲的液体生検による膵胆道がん患者と膵炎患者の鑑別 Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy
Christina Hartwig,Jan Müller,Hagen Klett,Dina Kouhestani,Anke Mittelstädt,Anna Anthuber,Paul David,Maximilian Brunner,Anne Jacobsen,Karolina Glanz,Izabela Swierzy,Lotta Roßdeutsch,Bettina Klösch,Robert Grützmann,Timo Wittenberger,Kai Sohn & Georg F. Weber
Molecular Cancer Published:02 February 2024
DOI:https://doi.org/10.1186/s12943-024-01943-x
Abstract
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.
消化器がん疾患における液体生検の現在の応用—早期がん検出から個別化がん治療まで Current Applications of Liquid Biopsy in Gastrointestinal Cancer Disease—From Early Cancer Detection to Individualized Cancer Treatment
Paul David,Anke Mittelstädt,Dina Kouhestani,Anna Anthuber,Christoph Kahlert,Kai Sohn andGeorg F. Weber
Cancers Published: 23 March 2023
DOI:https://doi.org/10.3390/cancers15071924
Simple Summary
Gastrointestinal (GI) cancers are a common cancer, affecting both men and women, normally diagnosed through tissue biopsies in combination with imaging techniques and standardized biomarkers leading to patient selection for local or systemic therapies. Liquid biopsies (LBs)—due to their non-invasive nature as well as low risk—are the current focus of cancer research and could be a promising tool for early cancer detection and treatment surveillance, thus leading to better patient outcomes. In this review, we provide an overview of different types of LBs enabling early detection and monitoring of GI cancers and their clinical application.
Abstract
Worldwide, gastrointestinal (GI) cancers account for a significant amount of cancer-related mortality. Tests that allow an early diagnosis could lead to an improvement in patient survival. Liquid biopsies (LBs) due to their non-invasive nature as well as low risk are the current focus of cancer research and could be a promising tool for early cancer detection. LB involves the sampling of any biological fluid (e.g., blood, urine, saliva) to enrich and analyze the tumor’s biological material. LBs can detect tumor-associated components such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs). These components can reflect the status of the disease and can facilitate clinical decisions. LBs offer a unique and new way to assess cancers at all stages of treatment, from cancer screenings to prognosis to management of multidisciplinary therapies. In this review, we will provide insights into the current status of the various types of LBs enabling early detection and monitoring of GI cancers and their use in in vitro diagnostics.
