title: Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer: a prognostic entity.
abstract: Patients with malignancies often possess increased concentrations of cell-free serum DNA. In this study, we investigated serum DNA levels in each 45 patients with bladder cancer (BCA) undergoing radical cystectomy and with benign prostate hyperplasia. A quantitative real-time PCR was used to amplify a 124 bp (PTGS2; mostly apoptotic origin) and a 271 bp (Reprimo; mostly necrotic origin) DNA fragment. Changes in the origin of DNA fragments were specified as the Apoptosis Index (AI, ratio of 124 bp/271 bp fragments). Small and large fragments were increased (p<0.001 and p=0.041) in BCA patients. The AI increase suggests that DNA fragmentation was mostly (p<0.001) caused by apoptosis. High levels of small DNA fragments distinguished between BCA and BPH with high sensitivity (96%) and moderate specificity (62%). DNA levels and the AI were not correlated with clinicopathological parameters. However, an increased AI was correlated with BCA-specific mortality in a multivariate analysis (p=0.011) indicating that the AI is an independent prognostic factor. Thus, cell-free DNA seems to be a useful prognostic marker in patients with BCA.
authors.affiliation: Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. joerg.ellinger@ukb.uni-bonn.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Nadja
authors.initials: N
authors.lastname: Ellinger
authors.forename: Philip
authors.initials: P
authors.lastname: Kahl
authors.forename: Frank G
authors.initials: FG
authors.lastname: Perabo
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Alexander von
authors.initials: Av
authors.lastname: Ruecker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000097:blood*; D004247:DNA / Q000097:blood*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011470:Prostatic Hyperplasia / Q000097:blood; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D044967:Serum; D001749:Urinary Bladder Neoplasms / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA