前列腺组织mtDNA突变对前列腺癌恶性程度的影响

Effect of mtDNA Mutation on Tumor Malignant Degree in Patients with Prostate Cancer

目的:了解前列腺癌患者mtDNA突变频率以及其对前列腺癌恶性程度的影响。方法:选2006年10月～2008年3月经历前列腺穿刺活检或前列腺癌根治的130例前列腺癌患者作为研究组,年龄60～97(70.1±2.4)岁;26例前列腺增生患者为对照组,年龄60～92(69.8±2.1)岁。采用PCR方法检测前列腺组织线粒体DNA4977(mtDNA^(4977))缺失率,对所有患者进行组织病理学Gleason评分。结果:研究组98例发生mtDNA^(4977)缺失(75.4%),对照组3例发生mtDNA^(4977)缺失(11.5%),差异有统计学意义(P<0.01)。前列腺癌组发生mtDNA^(4977)突变的患者Gleason评分(7.6±2.4)显著高于无突变患者(6.2±1.1,P<0.01)。应用对数回归分析证实Gleason评分(OR=1.452,95%CI:1.149-1.833)与年龄(OR=1.086,95%CI:1.010-1.167)是mtDNA^(4977)缺失突变的独立预测因子,敏感性和特异性分别是75.4%和88.5%,准确率为78%(121/156),代表mtDNA^(4977)缺失的ROC曲线下面积为0.82。结论:mtDNA^(4977)缺失突变率可能对辨别前列腺增生和前列腺癌有帮助,可作为前列腺癌恶性程度评估的一个生物标记物。

Objective：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, 60-97 years） undergoing either prostate biopsy or radical prostatectomy between October 2006 and March 2008 were included. Additionally, 26 patients with benign prostatic hyperplasia （mean age, 69.8±2.1; range, 60 to 92 years） were included as a control group. Mitochondrial DNA （mtDNA^4977 ） deletion mutations were identified by PCR. Gleason scores were determined by histopathology in all cases. Results： Among the 130 Pca samples vs. 26 BPH samples, mtDNA^4977 deletion mutation was detected in 98 cases （98/130, 75.4%） vs. in 3 cases （3/26, 11.5%）, respectively, indicating a significant difference （P〈0.01）. There was a significantly higher prevalence of the mtDNA497r deletion mutation in patients with prostate cancer （98/130, 75.4%） compared to patients with BPH （3/26, 11. 5 % ; P〈0.01 ）. Gleason scores were significantly higher in the group of cancer patients 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=1.452, 95%CI： 1. 149-1. 833） and age （OR=1.086, 95%CI： 1.010-1.167） are both independent predictors of the mtDNA497r deletion mutations. In the comparison of BPH and PCA, the positive pre dictive value of the mtDNA^4977 deletion of the specimens in correctly calling the presence of a malignant focus was 97% （98/101）. The sensitivity and specificity were 75. 4% and 88.5%, respectively, and accuracy was 78% （121/156）. The area under the ROC curve was fairly good, at 0.82 for the mtDNA^4977 deletion. Conclusions：mtDNA^4977 deletion mutation frequency may be useful in defining BPH and PCa tissues, which can be used as a biomar ker in malignant degree appraisal in Pca patients. These results demonstrate that mtDNA^4977 deletion may be a po tentially useful biomarker in predicting the degree of malignancy of prostatic lesions.