Noninvasive detection of any-stage cancer using free glycosaminoglycans
Artikel i vetenskaplig tidskrift, 2022
Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.
metabolomics
liquid biopsy
cancer biomarkers
prognosis
multi-cancer early detection
Författare
Sinisa Bratulic
Chalmers, Biologi och bioteknik, Systembiologi
Angelo Limeta
Chalmers, Biologi och bioteknik, Systembiologi
Saeed Dabestani
Lunds universitet
Centralsjukhuset Kristianstad
Helgi Birgisson
Akademiska Sjukhuset
Gunilla Enblad
Uppsala universitet
Karin Stålberg
Uppsala universitet
Göran Hesselager
Akademiska Sjukhuset
Michael Häggman
Akademiska Sjukhuset
Martin Höglund
Akademiska Sjukhuset
Oscar E. Simonson
Akademiska Sjukhuset
Peter Stålberg
Akademiska Sjukhuset
Henrik Lindman
Uppsala universitet
Anna Bång-Rudenstam
Lunds universitet
Matias Ekstrand
Wallenberg Lab.
Gunjan Kumar
Vancouver Prostate Centre
University of British Columbia (UBC)
Ilaria Cavarretta
IRCCS Ospedale San Raffaele
Massimo Alfano
IRCCS Ospedale San Raffaele
Francesco Pellegrino
IRCCS Ospedale San Raffaele
Thomas Mandel Clausen
University of California
Ali Salanti
Köpenhamns universitet
Copenhagen University Hospital
F. Maccari
Universita Degli Studi Di Modena E Reggio Emilia
F. Galeotti
Universita Degli Studi Di Modena E Reggio Emilia
N. Volpi
Universita Degli Studi Di Modena E Reggio Emilia
Mads Daugaard
Vancouver Prostate Centre
University of British Columbia (UBC)
M. Belting
Lunds universitet
Sven Lundstam
Göteborgs universitet
Ulrika Stierner
Göteborgs universitet
Jan Nyman
Göteborgs universitet
Bengt Bergman
Göteborgs universitet
P. H. Edqvist
Uppsala universitet
Max Levin
Wallenberg Lab.
Göteborgs universitet
Andrea Salonia
Università Vita-Salute San Raffaele
IRCCS Ospedale San Raffaele
Henrik Kjölhede
Göteborgs universitet
Sahlgrenska universitetssjukhuset
Eric Jonasch
University of Texas MD Anderson Cancer Center
Jens B Nielsen
BioInnovation Institute
Chalmers, Biologi och bioteknik, Systembiologi
Francesco Gatto
Karolinska Institutet
Chalmers, Biologi och bioteknik, Systembiologi
Proceedings of the National Academy of Sciences of the United States of America
0027-8424 (ISSN) 1091-6490 (eISSN)
Vol. 119 50Ämneskategorier (SSIF 2011)
Klinisk laboratoriemedicin
Urologi och njurmedicin
Cancer och onkologi
DOI
10.1073/pnas.2115328119
PubMed
36469776