Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.
BACKGROUND
Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker.


METHODS
In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined.


RESULTS
The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively.


CONCLUSIONS
Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer.
Department of Urology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Antonin
A
Brisuda
Eva
E
Pazourkova
Viktor
V
Soukup
Ales
A
Horinek
Jan
J
Hrbáček
Otakar
O
Capoun
Iveta
I
Svobodova
Sarka
S
Pospisilova
Marie
M
Korabecna
Jaroslav
J
Mares
Tomáš
T
Hanuš
Marek
M
Babjuk
D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D002474:Cell-Free System; D004247:DNA / Q000032:analysis / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016482:Urinalysis / Q000592:standards*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*
D014408:Biomarkers, Tumor; D004247:DNA