Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy

Abstract

To investigate the role of circulating mitochondrial DNA (mtDNA) in patients with localized prostate cancer, as recent reports show that patients with advanced cancer have increased levels of mtDNA. DNA was isolated from the serum of 100 patients with prostate cancer and 18 with benign prostate hyperplasia (BPH). A quantitative real-time polymerase chain reaction was used to amplify 79 bp and 230 bp fragments of the mitochondrial 16s-RNA gene, the short fragment representing total mtDNA, including mtDNA truncated by apoptosis, and the long fragment representing mostly mtDNA from other cell death entities. mtDNA integrity was defined as the ratio of long to short mtDNA fragments. The short and long mtDNA levels, and mtDNA integrity, were similar in patients with BPH and cancer (P = 0.940, 0.211 and 0.441, respectively), and were not correlated with clinical or pathological variables, e.g. age, prostate-specific antigen (PSA) level, cT stage, pT stage, seminal vesicle infiltration, lymph node invasion, or Gleason score (P = 0.075 to 0.961). However, patients with high levels of short mtDNA (>75th percentile) had a greater risk of PSA progression and this variable was the strongest predictor of PSA recurrence in a multivariate Cox analysis (P = 0.023; hazard ratio 0.31; 95% confidence interval 0.113-0.851). Circulating mtDNA levels did not distinguish between patients with prostate cancer or BPH. However, there was a significant increase in short mtDNA fragments in patients with early PSA recurrence after radical prostatectomy.