title: Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis.
abstract: BACKGROUND
  To date, no reliable serum marker for clear cell renal cell carcinoma (CCRCC) is available. The aim of this study was to evaluate the putative significance of circulating 20S proteasome levels.
  
  
  METHODS
  Preoperative 20S proteasome serum levels were determined in 113 CCRCC patients and 15 healthy controls by a sandwich enzyme-linked immunosorbent assay. Associations with CCRCC, pathological variables, disease-specific survival (DSS), and response to sunitinib were evaluated.
  
  
  RESULTS
  Median 20S proteasome levels were higher in CCRCC patients than in healthy controls (4.66 vs 1.52 μg ml(-1), P<0.0001). The area under the receiver operating characteristics curve curve was 87.1%. The 20S proteasome levels were associated with symptoms (P=0.0008), distant metastases (P=0.0011), grade (P=0.0247), and necrosis (P=0.0462). The 20S proteasome levels were identified as a prognostic factor for DSS in both univariable (hazards ratio 1.21, P<0.001) and multivariable (hazards ratio 1.17, P=0.0015) survival analysis. In patients responding to sunitinib, 20S proteasome levels were lower than in patients with stable disease and progressive disease.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that increased 20S proteasome levels are associated with CCRCC, advanced disease, and poor prognosis. Routine use of this marker may allow better diagnosis, risk stratification, risk-adjusted follow-up, and identification of patients with a greater likelihood of response to targeted therapy.
authors.affiliation: Department of Urology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria.
authors.forename: M
authors.initials: M
authors.lastname: de Martino
authors.forename: K
authors.initials: K
authors.lastname: Hoetzenecker
authors.forename: H J
authors.initials: HJ
authors.lastname: Ankersmit
authors.forename: G A
authors.initials: GA
authors.lastname: Roth
authors.forename: A
authors.initials: A
authors.lastname: Haitel
authors.forename: M
authors.initials: M
authors.lastname: Waldert
authors.forename: T
authors.initials: T
authors.lastname: Klatte
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000097:blood*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D046988:Proteasome Endopeptidase Complex; D000077210:Sunitinib