Evaluation of two mitochondrial DNA biomarkers for prostate cancer detection

Article type: Research Article

Authors: Maragh, Samantha^{a; *} | Veltri, Robert W.^b | Lund, Steven P.^c | Mangold, Leslie^b | Isharwal, Sumit^b | Christudass, Christhunesa S.^d | Partin, Alan W.^b | Humphreys, Elizabeth B.^b | Sorbara, Lynn^e | Srivastava, Sudhir^e | Wagner, Paul D.^e

Affiliations: [a] Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA | [b] Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [c] Statistical Engineering Division, National Institute of Standards and Technology, Gaithersburg, MD, USA | [d] Department of Neurological Sciences, Christian Medical College, Vellore, Tamilnadu, India | [e] Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA

Correspondence: [*] Corresponding author: Samantha Maragh, 100 Bureau Dr, MS 8312, Gaithersburg MD 20899, USA. Tel.: +1 301 975 4947; Fax: +1 301 330 3447; E-mail:[email protected]

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.

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

DOI: 10.3233/CBM-150518

Journal: Cancer Biomarkers, vol. 15, no. 6, pp. 763-773, 2015