title: Aberrant methylation of RARbeta2 and APC genes in voided urine as molecular markers for early detection of bilharzial and nonbilharzial bladder cancer.
abstract: BACKGROUND
  Bladder cancer cells illustrate major disruptions in their DNA methylation patterns as compared with normal ones. Authors aimed to identify epigenetic molecular markers in urine for early detection of bladder cancer.
  
  
  METHODS
  We retrospectively analyzed the methylation status of RARβ(2) and APC genes in urine samples from 210 bladder cancer patients, 61 patients with benign urological diseases, and 49 healthy volunteers by using methylation-specific PCR.
  
  
  RESULTS
  Methylated RARβ(2) and APC were significantly higher in bladder cancer patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathologic factors; however, they were detected in all grades and stages. Among the 128 patients with bilharzial bladder cancer, 94 (73.4%) showed methylated RARβ(2) and 86 (67.2%) showed methylated APC. Homoplasmic methylation pattern of both genes were only detected in bilharzial bladder cancer cases. Both sensitivities and specificities of the methylated genes for bladder cancer detection were superior to urine cytology and when altogether combined, the sensitivities improved to (91.8%), (93.5%), (91.9%), and (80.9%) in detection of: bladder cancer, non-muscle invasive bladder cancer, low-grade tumors, and bilharzial associated bladder cancer, respectively.
  
  
  CONCLUSIONS
  Thus, methylated RARβ(2) and APC genes might be valuable urinary molecular markers for early detection of bilharzial and nonbilharzial bladder cancer.
authors.affiliation: Oncology Diagnostic Unit, Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. dr_sanaa_eissa@yahoo.com
authors.forename: Sanaa
authors.initials: S
authors.lastname: Eissa
authors.forename: Menha
authors.initials: M
authors.lastname: Swellam
authors.forename: Inas M
authors.initials: IM
authors.lastname: El-Khouly
authors.forename: Samar K
authors.initials: SK
authors.lastname: Kassim
authors.forename: Hanan
authors.initials: H
authors.lastname: Shehata
authors.forename: Amal
authors.initials: A
authors.lastname: Mansour
authors.forename: Mohamed
authors.initials: M
authors.lastname: Esmat
authors.forename: Ahmed Ibrahim
authors.initials: AI
authors.lastname: Nossier
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Hamdy
authors.forename: Nahla M
authors.initials: NM
authors.lastname: Awad
authors.forename: Omar
authors.initials: O
authors.lastname: El-Ahmady
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000652:urine*; D005260:Female; D017491:Genes, APC; D006801:Humans; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012189:Retrospective Studies; D012548:Schistosoma haematobium / Q000302:isolation & purification; D012553:Schistosomiasis haematobia / Q000150:complications / Q000235:genetics / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000469:parasitology* / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018168:Receptors, Retinoic Acid; C540966:retinoic acid receptor, beta2, human