BACKGROUND: Cell-free serum DNA levels are increased in patients with cancer, and at least partially, these DNA fragments are derived from cancer cells.
A few reports indicated that methylated serum DNA in patients with bladder cancer (BCA) is a useful non-invasive biomarker. The purpose of this prospective multicenter study was to validate earlier studies.
MATERIALS AND METHODS: In total, 227 consecutive participants (non-muscle invasive BCA, n=75; muscle-invasive BCA, n=20; transurethral bladder resection (TURB) without BCA, n=48; benign disease, n=31; healthy individuals, n=53), were recruited for this study. Cell-free serum DNA was isolated and digested with methylation-sensitive restriction-enzymes (Bsh1236I, HpaII and HinP1I) to quantify the amount of methylated (TIMP3, APC, RARB, TIG1, GSTP1, p14, p16, PTGS2 and RASSF1A) DNA fragments.
RESULTS: The amount of methylated DNA was usually small (< 10%), and the methylation frequencies varied for different genes (e.g. frequent: TIMP3; moderate: APC, RARB, TIG1; infrequent: p16, PTGS2, p14, RASSF1A, GSTP1). Methylation levels at each gene site and the number of methylated genes were increased in BCA compared to healthy individuals, but were similar in BCA and patients with non-malignant disease. The number of methylated genes allowed for discrimination (62% sensitivity, 89% specificity) of BCA patients from healthy individuals. DNA hypermethylation was not correlated with advanced stage or grade in patients with BCA.
CONCLUSION: The detection of hypermethylated DNA in serum allows for discrimination of patients with BCA and healthy individuals, but there is no difference between patients with BCA and those with non-malignant disease, thereby limiting its value as a non-invasive biomarker.
Written by:
Hauser S, Kogej M, Fechner G, VON Pezold J, Vorreuther R, Lümmen G, Müller SC, Ellinger J. Are you the author?
Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Reference: Anticancer Res. 2013 Mar;33(3):779-84.
PubMed Abstract
PMID: 23482744
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