Noninvasive detection of any-stage cancer using free glycosaminoglycans
Multi-cancer early detection (MCED) is an emerging paradigm to curb cancer mortality by shifting the stage at diagnosis through a single test capturing all cancer types when still confined to their tissue of origin (stage I). Liquid biopsies based on genomic biomarkers could make MCED realistic, but limitations include 10% stage I sensitivity in validation studies ; the inability to detect specific types like gliomas ; complex assays ; and potential overdiagnosis.
Development of plasma, urine, and combined free GAGome MCED scores.
(A) Development study overview and summary of free GAGome analysis (Ntot = 979, 553 cancers vs. 426 healthy ; Nplasma = 517 cancers vs. 425 healthy ; Nurine = 220 cancers vs. 340 healthy ; Ncombined = 184 cancers vs. 339 healthy).
(B and C) Estimated means of plasma and urine GAGome features conditional on the cancer type (median Nplasma per cancer type = 30, range : 14–83 ; median Nurine = 50 per cancer type, range : 17–56). Dots signify credible deviations from healthy subjects. The vertical axis denotes independent and dependent GAGome features (measured in μg mL-1 [except for charge, which is a.u.] or %w/w, respectively).
The authors demonstrate the potential of free glycosaminoglycan profiles (GAGomes) as metabolic biomarkers for MCED across 14 cancer types. In a validation study, plasma and urine GAGomes doubled the stage I sensitivity reported by state-of-the-art genomics biomarkers and detected poor prognosis cancers. As such, this simple assay could accelerate MCED implementation.