title: Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma.
abstract: 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.
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gatto
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Volpi
authors.affiliation: Department of Translational Medicine Malmö, Center for Molecular Pathology, Lund University, Skåne University Hospital, 20502 Malmö, Sweden.
authors.forename: Helén
authors.initials: H
authors.lastname: Nilsson
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden.
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maruzzo
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Roma
authors.affiliation: Department of Translational Medicine Malmö, Center for Molecular Pathology, Lund University, Skåne University Hospital, 20502 Malmö, Sweden.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, 41345 Göteborg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Stierner
authors.affiliation: Department of Urology, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, 41345 Göteborg, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Lundstam
authors.affiliation: Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, 35128 Padova, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Basso
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden. Electronic address: nielsenj@chalmers.se.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000097:blood* / Q000652:urine*; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D006025:Glycosaminoglycans; D012333:RNA, Messenger