title: Serum cell-free DNA in renal cell carcinoma: a diagnostic and prognostic marker.
abstract: BACKGROUND
  Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell-free DNA.
  
  
  METHODS
  Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real-time polymerase chain reaction was used to assess total cell-free DNA (ring finger protein 185 [RNF185]) and CpG island methylation of Ras association domain family member 1A (RASSF1A) von Hippel-Lindau (VHL), prostaglandin-endoperoxidase synthase 2 (PTGS2), and P16 (cyclin-dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific survival were evaluated.
  
  
  RESULTS
  Total cell-free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes (P = .007). Total cell-free DNA levels were higher in patients with metastatic RCC (P < .001) and necrotic RCC (P = .003) and were associated with poorer disease-specific survival (P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score (P < .001) and categorized total cell-free DNA levels (P = .028) were retained as independent prognostic factors.
  
  
  CONCLUSIONS
  The current results indicated that cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell-free DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required.
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michela
authors.initials: M
authors.lastname: de Martino
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002474:Cell-Free System; D018899:CpG Islands; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D004247:DNA