title: Diagnostic and prognostic potential of circulating cell-free genomic and mitochondrial DNA fragments in clear cell renal cell carcinoma patients.
abstract: BACKGROUND
  There is inconsistent information about the clinical usefulness of circulating cell-free DNA (cfDNA) in plasma from clear cell renal cell cancer (RCC) patients. This is attributed to preanalytical, analytical, and clinical factors that were considered as far as possible in this study.
  
  
  METHODS
  cfDNA was extracted from EDTA plasma of healthy people (n=40), non-metastatic (n=145) and metastatic (n=84) RCC patients using the QIAamp Circulating Nucleic Acid Kit. Genomic and mitochondrial cfDNA concentrations were determined using qPCR of different cfDNA fragments (67-306bp). Their diagnostic and prognostic potential was estimated using receiver operating characteristics (ROC) and Cox regression analyses.
  
  
  RESULTS
  The 67bp and 180bp genomic cfDNA fragments did not differ between the three study groups while the 306bp fragment was lower in RCC patients than in controls. The mitochondrial cfDNA was higher in metastatic than in non-metastatic patients and controls. The cfDNA integrity indices decreased from controls to metastatic patients. Models built by logistic regression and Cox regression resulted in area under the ROC curves >0.75 and concordance indices of >0.800 in predicting recurrence-free survival and overall survival.
  
  
  CONCLUSIONS
  The study suggests that combinations of cfDNA markers have promising diagnostic and prognostic potential in RCC patients and are worth for further validation in future prospective multicenter studies.
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany; Department of Urology, Changzhou No.2 People's Hospital, Jiangsu, China.
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Rabenhorst
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ralla
authors.affiliation: Institute of Pathology, University Hospital Charité, Berlin, Germany.
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.affiliation: CONGEN Biotechnologie GmbH, Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Mergemeier
authors.affiliation: Department of Radiology, University Hospital Charité, Berlin, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Budach
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany; Department of Signal Transduction, Invasion and Metastasis of Epithelial Cells, Max Delbrück Center of Molecular Medicine, Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Fendler
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany. Electronic address: klaus.jung@charite.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis
chemical_list: D004272:DNA, Mitochondrial
keywords: Circulating cell-free DNA; Clear cell renal cell carcinoma; Diagnostic; Metastasis; Predictive models; Prognostic markers