title: Frequent methylation of RASSF1 and RARB in urine sediments from patients with early stage prostate cancer.
abstract: BACKGROUND. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. MATERIAL AND METHODS. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. RESULTS. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). CONCLUSIONS. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa.
authors.affiliation: Vilnius University, Čiurlionio, Lithuania.
authors.forename: Kristina
authors.initials: K
authors.lastname: Daniūnaitė
authors.forename: Artūras
authors.initials: A
authors.lastname: Berezniakovas
authors.forename: Feliksas
authors.initials: F
authors.lastname: Jankevičius
authors.forename: Arvydas
authors.initials: A
authors.lastname: Laurinavičius
authors.forename: Juozas R
authors.initials: JR
authors.lastname: Lazutka
authors.forename: Sonata
authors.initials: S
authors.lastname: Jarmalaitė
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine; D001706:Biopsy; D019175:DNA Methylation; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi