Glycosaminoglycan Profiling in Patients’ Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma
Francesco Gatto,
Nicola Volpi,
Helén Nilsson,
Intawat Nookaew,
Marco Maruzzo,
Anna Roma,
Martin E. Johansson,
Ulrika Stierner,
Sven Lundstam,
Umberto Basso,
Jens Nielsen
Affiliations
Francesco Gatto
Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden
Nicola Volpi
Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Helén Nilsson
Department of Translational Medicine Malmö, Center for Molecular Pathology, Lund University, Skåne University Hospital, 20502 Malmö, Sweden
Intawat Nookaew
Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden
Marco Maruzzo
Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy
Anna Roma
Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy
Martin E. Johansson
Department of Translational Medicine Malmö, Center for Molecular Pathology, Lund University, Skåne University Hospital, 20502 Malmö, Sweden
Ulrika Stierner
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, 41345 Göteborg, Sweden
Sven Lundstam
Department of Urology, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, 41345 Göteborg, Sweden
Umberto Basso
Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy
Jens Nielsen
Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden
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.
