Evaluation of two mitochondrial DNA biomarkers for prostate cancer detection

BACKGROUND: A 3.4kb deletion (3.4kb.) 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 3.4kb. 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 3.4kb Delta 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 3.4kb. 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.