title: Evaluation of two mitochondrial DNA biomarkers for prostate cancer detection.
abstract: BACKGROUND
  A 3.4kb deletion (3.4kbΔ ) in mitochondrial DNA (mtDNA) found in histologically normal prostate biopsy specimens has been reported to be a biomarker for the increased probability of prostate cancer. Increased mtDNA copy number is also reported as associated with cancer.
  
  
  OBJECTIVE
  Independent evaluation of these two potential prostate cancer biomarkers using formalin-fixed paraffin-embedded (FFPE) prostate tissue and matched urine and serum from a high risk cohort of men with and without prostate cancer.
  
  
  METHODS
  Biomarker levels were detected via qPCR.
  
  
  RESULTS
  Both 3.4kbΔ and mtDNA levels were significantly higher in cancer patient FFPE cores (p= 0.045 and p= 0.070 respectively at > 90% confidence). Urine from cancer patients contained significantly higher levels of mtDNA (p= 0.006, 64.3% sensitivity, 86.7% specificity). Combining the 3.4kbΔ and mtDNA gave better performance of detecting prostate cancer than either biomarker alone (FFPE 73.7% sensitivity, 65% specificity; urine 64.3% sensitivity, 100% specificity). In serum, there was no difference for any of the biomarkers.
  
  
  CONCLUSIONS
  This is the first report on detecting the 3.4kbΔ in urine and evaluating mtDNA levels as a prostate cancer biomarker. A confirmation study with increased sample size and possibly with additional biomarkers would need to be conducted to corroborate and extend these observations.
authors.affiliation: Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Maragh
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
authors.affiliation: Statistical Engineering Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Lund
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Mangold
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Isharwal
authors.affiliation: Department of Neurological Sciences, Christian Medical College, Vellore, Tamilnadu, India.
authors.forename: Christhunesa S
authors.initials: CS
authors.lastname: Christudass
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Humphreys
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Sorbara
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Wagner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D011446:Prospective Studies; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000652:urine; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D016482:Urinalysis
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers
keywords: 3.4kb deletion; EDRN; FFPE; NIST; Prostate; biomarker; cancer; mitochondrial DNA; serum; urine