Evaluation of two mitochondrial DNA biomarkers for prostate cancer detection

Samantha Maragh, Robert W. Veltri, Steven P. Lund, Leslie Mangold, Sumit Isharwal, Christhunesa S. Christudass, Alan W. Partin, Elizabeth B. Humphreys, Lynn Sorbara, Sudhir Srivastava, Paul D. Wagner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)763-773
Number of pages11
JournalCancer Biomarkers
Volume15
Issue number6
DOIs
StatePublished - Nov 24 2015

Keywords

  • 3.4kb deletion
  • EDRN
  • FFPE
  • NIST
  • Prostate
  • biomarker
  • cancer
  • mitochondrial DNA
  • serum
  • urine

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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