Effect of mtDNA mutation on tumor malignant degree in patients with prostate cancer

Abstract

Objectives. To understand mtDNA mutation frequency in patients with prostate cancer (Pca) and its effect on malignant degree of PCa.Methods. A total of 130 patients (mean age, 70.1 ± 2.4; range, 58–97 years) undergoing either prostate biopsy or radical prostatectomy between October 2006 and March 2008 were included. Additionally, 61 patients with benign prostatic hyperplasia (mean age, 69.9 ± 1.1; range, 60–92 years) were included as a control group. The normal cells were isolated from each prostate cancer specimen by microdissection. Mitochondrial DNA (mtDNA4977) deletion mutations were identified by polymerase chain reaction. Gleason scores were determined by histopathology.Results. Among the 130 Pca samples vs. 61 BPH samples, mtDNA4977 deletion mutation was detected in 98 cases (98/130, 75.4%) vs. in 9 cases (9/61, 14.7%) (P < 0.01, P = 0.001). There was a significantly higher prevalence of the mtDNA4977 deletion mutation in patients with prostate cancer compared to patients with BPH (P < 0.01). The incidence of the mtDNA4977 deletion in normal cells isolated from cancer specimen was 10.76% (14/130), which was significantly lower than that in prostate cancer group(P < 0.01). However, there was no significant difference versus BPH group (P > 0.5). Gleason scores were significantly higher in the group of patients with cancer with the mutation (7.6 ± 2.4), compared to those without the mutation (6.2 ± 1.1, P < 0.01). Logistic regression analysis demonstrated that Gleason scores (OR = 1.642, 95% CI: 1.232–2.183) and age (OR = 1.061, 95% CI: 1.041–1.082) are both independent predictors of the mtDNA4977 deletion mutations.Conclusions. mtDNA4977 deletion mutation frequency may be useful as a biomarker in malignant degree appraisal in patients with Pca.