Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker
Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker
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DOI：
10.1111/j.1464-410x.2008.08289.x
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发表时间：
2009-07-01
影响因子：
4.5
通讯作者：
Bastian, Patrick J.
中科院分区：
文献类型：
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作者：
Ellinger, Joerg;Albers, Peter;Bastian, Patrick J.
目的分析睾丸癌患者外周血中游离线粒体DNA(Mt DNA)水平升高的诊断和预后价值。从1毫升血清中提取循环DNA。用实时定量聚合酶链式反应分析线粒体特异性16S-RNA的79bp(mtDNA-79)和220bp(mtDNA-220)片段的水平。线粒体DNA完整性以线粒体DNA-2 2 2 0/mtDNA-79的比值表示。结果睾丸癌患者mtDNA-79和mtDNA-2 2 0水平显著高于正常人(P<0.001)。线粒体DNA完整性在患者和健康对照组中相似(P=0.435)。受试者操作员特征曲线分析显示，患者与健康人无细胞线粒体DNA(mtDNA-79)水平差异显著，敏感性为59.5%，特异性为94.3%(曲线下面积为0.787)。同时，mtDNA-79水平可用于区分31例甲胎蛋白、人绒毛膜促性腺激素、胎盘碱性磷酸酶和乳酸脱氢酶等常规标志物在正常范围内的患者和健康人，其敏感性为64.5%，特异性为91.4%(曲线下面积0.797)。无细胞mtDNA水平与任何临床病理变量(PT分期、淋巴结侵犯、血管侵犯、临床分期、国际生殖细胞癌症合作组织分类、肿瘤标志物；均P>；0.05)无关。结论睾丸癌患者的无细胞mtDNA水平较高，可能为睾丸异常患者的治疗提供有价值的信息，尤其是那些已建立的肿瘤标志物水平正常的患者。
OBJECTIVETo analyse the diagnostic and prognostic value of cell-free mitochondrial (mt) DNA in patients with testicular cancer, as increased levels of cell-free circulating mtDNA have been reported in patients with cancer.PATIENTS, SUBJECTS AND METHODSIn all, 74 patients with testicular cancer (seminoma in 39, nonseminoma in 35) and 35 healthy individuals were included in the study. Circulating DNA was isolated from 1 mL of serum. A quantitative real-time polymerase chain reaction was used to analyse the levels of a 79-bp (mtDNA-79) and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mtDNA integrity was expressed as the ratio of mtDNA-220 to mtDNA-79.RESULTSmtDNA-79 and mtDNA-220 levels were significantly (P < 0.001) greater in patients with testicular cancer than in healthy individuals. The mtDNA integrity was similar in patients and healthy controls (P = 0.435). Receiver operator characteristic curve analysis showed that cell-free mtDNA (mtDNA-79) levels distinguished, with a sensitivity of 59.5% and a specificity of 94.3%, between patients and healthy individuals (area under curve, 0.787). Also, mtDNA-79 levels could be used to distinguish between patients (31) with conventional markers (alpha-fetoprotein, human chorionic gonadotrophin, placental alkaline phosphatase and lactate dehydrogenase) within normal ranges and healthy individuals, with a sensitivity of 64.5% and specificity of 91.4% (area under curve 0.797). Cell-free mtDNA levels were not correlated with any clinicopathological variable (pT stage, lymph node invasion, vascular invasion, clinical stage, International Germ Cell Cancer Collaborative Group classification, tumour markers; all P > 0.05).CONCLUSIONCell-free mtDNA levels are greater in patients with testicular cancer and might provide valuable information for managing patients with testicular anomalies, especially those with normal levels of established tumour markers.