Prostate cancer detection through unbiased capture of methylated cell-free DNA.

Autor:	Lleshi E; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.; Department of Engineering, University of Cambridge, Cambridge, UK., Milne-Clark T; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Lee Yu H; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Martin HW; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Hanson R; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Lach R; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Rossi SH; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Riediger AL; University Hospital Heidelberg, 69120 Heidelberg, Germany.; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany., Görtz M; University Hospital Heidelberg, 69120 Heidelberg, Germany., Sültmann H; Division of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany., Flewitt A; Department of Engineering, University of Cambridge, Cambridge, UK., Lynch AG; School of Mathematics and Statistics, University of St Andrews, St Andrews KY16 9SS, UK.; School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK., Gnanapragasam VJ; Department of Surgery, University of Cambridge, Addenbrooke's Hospital Site, Cambridge, UK., Massie CE; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK., Dev HS; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Jun 20; Vol. 27 (7), pp. 110330. Date of Electronic Publication: 2024 Jun 20 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110330
Abstrakt:	Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication. Competing Interests: The authors do not claim any competing interest in this work. (© 2024 The Authors.)
Databáze:	MEDLINE
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