Evaluation of two mitochondrial DNA biomarkers for prostate cancer detection

Cancer Biomark. 2015;15(6):763-73. doi: 10.3233/CBM-150518.


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.

Keywords: 3.4kb deletion; EDRN; FFPE; NIST; Prostate; biomarker; cancer; mitochondrial DNA; serum; urine.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / urine
  • Female
  • Follow-Up Studies
  • Genetic Markers*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Paraffin Embedding
  • Prognosis
  • Prospective Studies
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / urine
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Urinalysis


  • DNA, Mitochondrial
  • Genetic Markers