Noninvasive detection of any-stage cancer using free glycosaminoglycans
Journal article, 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

Author

Sinisa Bratulic

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Angelo Limeta

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Saeed Dabestani

Lund University

Kristianstad Central Hospital

Helgi Birgisson

Akademiska Sjukhuset

Gunilla Enblad

Uppsala University

Karin Stålberg

Uppsala University

Göran Hesselager

Akademiska Sjukhuset

Michael Häggman

Akademiska Sjukhuset

Martin Höglund

Akademiska Sjukhuset

Oscar E. Simonson

Akademiska Sjukhuset

Peter Stålberg

Akademiska Sjukhuset

Henrik Lindman

Uppsala University

Anna Bång-Rudenstam

Lund University

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

University of Copenhagen

Copenhagen University Hospital

F. Maccari

University of Modena and Reggio Emilia

F. Galeotti

University of Modena and Reggio Emilia

N. Volpi

University of Modena and Reggio Emilia

Mads Daugaard

Vancouver Prostate Centre

University of British Columbia (UBC)

M. Belting

Lund University

Sven Lundstam

University of Gothenburg

Ulrika Stierner

University of Gothenburg

Jan Nyman

University of Gothenburg

Bengt Bergman

University of Gothenburg

P. H. Edqvist

Uppsala University

Max Levin

Wallenberg Lab.

University of Gothenburg

Andrea Salonia

Università Vita-Salute San Raffaele

IRCCS Ospedale San Raffaele

Henrik Kjölhede

University of Gothenburg

Sahlgrenska University Hospital

Eric Jonasch

University of Texas MD Anderson Cancer Center

Jens B Nielsen

BioInnovation Institute

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Francesco Gatto

Karolinska Institutet

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 119 50

Subject Categories

Clinical Laboratory Medicine

Urology and Nephrology

Cancer and Oncology

DOI

10.1073/pnas.2115328119

PubMed

36469776

More information

Latest update

10/26/2023