Glycosaminoglycan Profiling in Patients’ Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma | Zendy

Francesco Gatto | Zendy; Nicola Volpi | Zendy; Helén Nilsson | Zendy; Intawat Nookaew | Zendy; Marco Maruzzo | Zendy; Anna Roma | Zendy; Martin Johansson | Zendy; Ulrika Stierner | Zendy; Sven Lundstam | Zendy; Umberto Basso | Zendy; Jens Nielsen | Zendy

Open Access

Glycosaminoglycan Profiling in Patients’ Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma

Author(s) -

Francesco Gatto,

Nicola Volpi,

Helén Nilsson,

Intawat Nookaew,

Marco Maruzzo,

Anna Roma,

Martin Johansson,

Ulrika Stierner,

Sven Lundstam,

Umberto Basso,

Jens Nielsen

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.04.056

Subject(s) - clear cell renal cell carcinoma , glycosaminoglycan , renal cell carcinoma , biomarker , reprogramming , cell , cancer research , metastasis , gene expression profiling , urine , extracellular , biology , medicine , cancer , endocrinology , microbiology and biotechnology , biochemistry , gene expression , gene

Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis.

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