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Multi-modal cell-free DNA genomic and fragmentomic patterns enhance cancer survival and recurrence analysis

2023; Elsevier BV; Volume: 5; Issue: 1 Linguagem: Inglês

10.1016/j.xcrm.2023.101349

2666-3791

Norbert Moldován, Ymke van der Pol, Tom van den Ende, Dries Boers, Sandra A.W.M. Verkuijlen, Aafke Creemers, Jip Ramaker, Trang T. Vu, Sanne Bootsma, Kristiaan Lenos, Louis Vermeulen, Marieke F. Fransen, D. Michiel Pegtel, Idris Bahce, Hanneke W. M. van Laarhoven, Florent Moulière,

Genetic factors in colorectal cancer

The structure of cell-free DNA (cfDNA) is altered in the blood of patients with cancer. From whole-genome sequencing, we retrieve the cfDNA fragment-end composition using a new software (FrEIA [fragment end integrated analysis]), as well as the cfDNA size and tumor fraction in three independent cohorts (n = 925 cancer from >10 types and 321 control samples). At 95% specificity, we detect 72% cancer samples using at least one cfDNA measure, including 64% early-stage cancer (n = 220). cfDNA detection correlates with a shorter overall (p = 0.0086) and recurrence-free (p = 0.017) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n = 396 cancer, 90 controls) achieve a detection accuracy of 82% and area under the receiver operating characteristic curve of 0.96. In conclusion, harnessing the biological features of cfDNA can improve, at no extra cost, the diagnostic performance of liquid biopsies.