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Article type: Research Article
Authors: Maragh, Samanthaa; * | Veltri, Robert W.b | Lund, Steven P.c | Mangold, Leslieb | Isharwal, Sumitb | Christudass, Christhunesa S.d | Partin, Alan W.b | Humphreys, Elizabeth B.b | Sorbara, Lynne | Srivastava, Sudhire | 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:Samantha@nist.gov
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
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