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首页> 外文期刊>Urologic oncology >Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies
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Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies

机译:血清中线粒体DNA循环:泌尿系统恶性肿瘤患者的通用诊断生物标志物

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摘要

Objective: Cell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients. Patients and methods: Cell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mitochondrial DNA integrity (mtDNA-integrity) was defined as ratio of mtDNA-220 to mtDNA-79 fragments. Results: In healthy controls, mtDNA-79 levels were increased in male volunteers; mtDNA-230 levels and mtDNA-integrity were correlated with age. Neither mtDNA levels nor mtDNA-integrity were correlated with age or gender in cancer patients. Circulating mtDNA-79 (median 8.75 × 10 6 vs. 0.43 × 10 6 copies/ml) and mtDNA-230 (8.11 × 10 6 vs. 0.27 × 10 6 copies/ml) levels were significantly increased in cancer patients and allowed sensitive (84%) and specific (97%) discrimination from healthy controls. mtDNA levels were unequally distributed among the different cancer entities (mtDNA-79: BCA 9.54 × 10 6 vs. RCC 6.69 × 10 6 vs. CaP 4.48 × 10 6 copies/ml; mtDNA-230: BCA 9.78 × 10 6 vs. RCC 6.74 × 10 6 vs. CaP 1.94 × 10 6 copies/ml). The mtDNA-integrity was increased in RCC and BCA patients compared to control subjects and CaP patients. Serum mtDNA-integrity was correlated with pathological stage in RCC and with tumor grade in BCA patients. Conclusion: Circulating mtDNA levels are associated with gender and age in healthy individuals, but not in cancer patients. Quantification of circulating mtDNA may help identify patients with urologic malignancies.
机译:目的:无细胞循环线粒体DNA(mtDNA)已被提议作为癌症患者的通用诊断和预后生物标志物。患者和方法:从1 ml血清中分离出无细胞DNA,这些血清来自患有膀胱癌(BCA,n = 33),肾细胞癌(RCC,n = 33)和前列腺癌(CaP,n = 23)的患者,以及与健康个体相比(n = 79)。实时定量PCR用于分析线粒体特异性16S-RNA的79 bp(mtDNA-79)和220 bp(mtDNA-220)片段的水平。线粒体DNA完整性(mtDNA完整性)定义为mtDNA-220与mtDNA-79片段的比率。结果:在健康对照中,男性志愿者的mtDNA-79水平升高; mtDNA-230水平和mtDNA完整性与年龄相关。癌症患者的mtDNA水平和mtDNA完整性均与年龄或性别无关。癌症患者的循环mtDNA-79(中位数为8.75×10 6 vs. 0.43×10 6个拷贝/ ml)和mtDNA-230(8.11×10 6对0.27×10 6个拷贝/ ml)的水平显着增加,并允许敏感84%)和来自健康对照的特定(97%)歧视。 mtDNA水平在不同癌症实体之间分布不均(mtDNA-79:BCA 9.54×10 6 vs. RCC 6.69×10 6 vs. CaP 4.48×10 6个拷贝/ ml; mtDNA-230:BCA 9.78×10 6 vs. RCC 6.74×10 6 vs. CaP 1.94×10 6拷贝/ ml)。与对照组和CaP患者相比,RCC和BCA患者的mtDNA完整性增加。血清mtDNA的完整性与RCC的病理分期和BCA患者的肿瘤分级有关。结论:健康个体的循环mtDNA水平与性别和年龄有关,而在癌症患者中则不相关。循环mtDNA的定量可能有助于识别患有泌尿系统恶性肿瘤的患者。

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