Detection of any-stage cancer using plasma and urine glycosaminoglycans.

• DOI: 10.1200/jco.2021.39.15_suppl.3034
• Publication Date: 2021-06-02T14:00:38Z
• Authors: Francesco Gatto; Sinisa Bratulic; Ilaria Teresa Rit...; Massimo Alfano; Francesca Maccari; Fabio Galeotti; Nicola Volpi; Per-Henrik Edqvist; Max Levin; Jan Nyman; Bengt Bergman; Andrea Salonia; Sven Lundstam; Ulrika Stierner; Henrik Kjölhede; Jens Nielsen
• Keywords: Liquid biopsy

3034 Background: Non-invasive liquid biopsies promise to enable early cancer detection and improve patient outcomes. However, virtually all rely on genomic biomarkers, with limited sensitivity early-stage tumors poor of cancers shedding little cell-free DNA, like genitourinary or brain tumors. Here, we explored the use plasma urine glycosaminoglycan (GAGs) profiles, GAGomes, as biomarkers reflective tumor metabolism serve an alternative pan-cancer biopsy. Methods: In this case-control study, enrolled retrospective prospective cohorts from Sweden Italy. Included cases were treatment-naïve early-stage/low-grade metastatic/high-grade across 14 histological types. controls healthy 22-78 y/o adults no history cancer. We measured GAGomes – encompassing 17 chondroitin sulfate (CS), heparan (HS), hyaluronate (HA) disaccharides - using a standardized UHPLC-MS/MS-based kit in central blind laboratory. tested top GAGome features different Bayesian estimation. These used design one GAG score for binary classification vs. control discovery set. computed area-under-the-curve (AUC), at 98% specificity each validation A subset analysis was performed only. survival records, multivariable Cox regression estimate hazard ratio (HR) overall (OS) adjusted type, age, gender. Results: 753 samples (460 types, median age = 66 y/o, 51% female 293 adults, 58 57% female) 559 (219 5 69 23% 340 56 60% female). set, had AUC 0.80 (95% CI: 0.74-0.85, 124 types 184 controls) while 0.82 0.78-0.86, 153 282 controls). 0.78 0.71-0.84, 95 156 35% specificity. The 0.84 0.79-0.88, 178 140 41% cancers, 0.72 urine, respectively. scores independent predictors OS regardless type (HR 1.39, p 0.005 [ N 283, 11 67 deaths, follow-up months] HR 1.53, 0.016 161, 4 32 15 months]). Conclusions: sensitive non-invasive metabolic any-stage cancer, including