Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer.
OBJECTIVE
Increased levels of cell-free circulating DNA have been described in various malignancies as a diagnostic and prognostic biomarker. We analyzed the significance of cell-free DNA in patients with testicular cancer.


METHODS
Cell-free DNA was isolated from the serum of 74 patients with testicular cancer, including 39 with seminoma and 35 with nonseminoma, and 35 healthy individuals. Real-time polymerase chain reaction was used to quantify a 106, a 193 and a 384 actin-beta DNA fragment. DNA integrity is expressed as the ratio of large (193 or 384 bp) to short (106 bp) DNA fragments.


RESULTS
Actin-beta-106/193/384 fragment levels were significantly increased in patients with cancer compared to those in healthy individuals (each p <0.001). DNA integrity was significantly decreased in patients with cancer (p <0.001). Cell-free DNA fragment levels were not different when comparing patients with nonseminoma and seminoma (p >0.24). ROC analysis demonstrated that cell-free DNA levels distinguished patients with cancer from healthy individuals with 87% sensitivity and 97% specificity. Even in 31 patients in whom the established serum tumor markers alpha-fetoprotein, human chorionic gonadotropin, placental alkaline phosphatase and lactate dehydrogenase were normal cell-free DNA levels allowed us to distinguish between patients with cancer and healthy individuals with 84% sensitivity and 97% specificity. Cell-free DNA levels were more frequently increased in patients with clinical stage 3 than in patients with stage 1 or 2 disease (p <0.046).


CONCLUSIONS
Cell-free DNA levels are increased in patients with testicular cancer and they allow the accurate discrimination of healthy individuals. The high sensitivity of cell-free DNA could facilitate the management of testicular cancer, especially in patients with conventional tumor markers that are not increased.
Ellinger
Jörg
J
Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Wittkamp
Volker
V
Albers
Peter
P
Perabo
Frank G E
FG
Mueller
Stefan C
SC
von Ruecker
Alexander
A
Bastian
Patrick J
PJ
D000293:Adolescent; D000328:Adult; D004247:DNA / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000175:diagnosis*; D013736:Testicular Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
D004247:DNA