Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker.
OBJECTIVE
To 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.


METHODS
In 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.


RESULTS
mtDNA-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).


CONCLUSIONS
Cell-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.
Ellinger
Jörg
J
Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. joerg.ellinger@ukb.uni-bonn.de
Albers
Peter
P
Müller
Stefan C
SC
von Ruecker
Alexander
A
Bastian
Patrick J
PJ
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000097:blood / Q000175:diagnosis*; D055815:Young Adult
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial