title: Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma.
abstract: BACKGROUND
  The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic-targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans (GAGs) aggregated into diagnostic scores correlated with ccRCC prognosis.
  
  
  METHODS
  Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled, and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous ("Low" vs. "High") or a continuous variable in a multivariate survival analysis.
  
  
  RESULTS
  The survival difference between "High"- vs. "Low"-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3 vs. 100%,p= 3 × 10-4and 2-year OS rate = 73.3 vs. 100%,p= 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60 vs. 84%,p= 0.0591 and 2-year OS rate = 66.7 vs. 90%,p= 0.0206). In multivariate analysis, the urine biomarker score as a continuous variable was an independent predictor of PFS [hazard ratio (HR): 4.62, 95% CI: 1.66-12.83,p= 0.003] and OS (HR: 10.13, 95% CI: 1.80-57.04,p= 0.009).
  
  
  CONCLUSIONS
  This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted.
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology , Göteborg , Sweden.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gatto
authors.affiliation: Medical Oncology Unit 1, IOV Istituto Oncologico Veneto (IRCSS) , Padova , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maruzzo
authors.affiliation: Medical Oncology Unit 1, IOV Istituto Oncologico Veneto (IRCSS) , Padova , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Magro
authors.affiliation: Medical Oncology Unit 1, IOV Istituto Oncologico Veneto (IRCSS) , Padova , Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Basso
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology , Göteborg , Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
keywords: kidney cancer; molecular biomarkers; prognostic biomarkers; systems medicine