Metabolic reprogramming is a hallmark of cancer — yet metabolism remains an under-investigated source of biomarkers. By overlaying genome-wide omics data onto the largest reconstruction of the human metabolic network, we identified glycosaminoglycan (GAG) disaccharides as the most deregulated panel of metabolites in cancer. We call their collective profile the GAGome.
Glycosaminoglycans (GAGs) are linear, sulfated polysaccharides found in every tissue, where they organize the extracellular matrix (ECM) and tune cell signaling. Unlike proteins, their disaccharide chains are not template-encoded but assembled and edited by a coordinated set of enzymes — transferases that initiate and elongate the chains, sulfotransferases and epimerases that modify them, sulfatases that edit them after synthesis, and glycosidases that cleave them. This structure — the disaccharide composition, sulfation pattern, and chain length — determines which growth factors, cytokines, and receptors a GAG binds. In cancer, GAGs are remodelled across the core processes of tumour biology — angiogenesis, proliferation, invasion, immune evasion, and metastasis.
The three most abundant GAG classes in humans — chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronic acid (HA) — are all part of this remodelling: heparan sulfate is degraded to release matrix-bound growth factors, hyaluronic acid is fragmented into smaller bioactive oligosaccharides, and chondroitin sulfate is synthesized in greater amounts with shifts towards distinctive sulfation patterns. Together these shifts reshape the matrix signals involved in tumour progression. Because GAGs are continuously shed from tissue into circulation, this remodelling is not confined to the tumour, making the GAGome — specifically the collective profile of CS, HS, and HA disaccharides — an accessible systemic biomarker that provides a window into tissue remodelling over time.
Altered GAG profiles were first observed in the plasma and urine of renal cell carcinoma patients across all stages, from organ-confined to metastatic disease, and the same systemic shift was later seen across 14 cancer types — prompting the development of standardized UHPLC-MS/MS kits to measure the GAGome for translational research and diagnostic development.
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ISO 13485:2016 certified for Design, development and manufacture of in vitro diagnostic test kits and software for the measurement and interpretation of glycosaminoglycans (GAGs) in human biofluids
