1. Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies
- Author
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Ellinger, Jörg, Müller, David C., Müller, Stefan C., Hauser, Stefan, Heukamp, Lukas C., von Ruecker, Alexander, Bastian, Patrick J., and Walgenbach-Brunagel, Gisela
- Subjects
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MITOCHONDRIAL DNA , *SERUM , *BIOMARKERS , *CANCER prognosis , *CANCER patients , *PROSTATE cancer , *RENAL cell carcinoma , *UROLOGY - Abstract
Abstract: 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 × 106 vs. 0.43 × 106 copies/ml) and mtDNA-230 (8.11 × 106 vs. 0.27 × 106 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 × 106 vs. RCC 6.69 × 106 vs. CaP 4.48 × 106 copies/ml; mtDNA-230: BCA 9.78 × 106 vs. RCC 6.74 × 106 vs. CaP 1.94 × 106 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. [Copyright &y& Elsevier]
- Published
- 2012
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