title: RSPH9 methylation pattern as a prognostic indicator in patients with non-muscle invasive bladder cancer.
abstract: DNA methylation is a frequent and early epigenetic event with potential application as a biomarker for cancer detection and an indicator of disease evolution. The aim of the present study was to identify novel methylation markers for the prediction of patient outcomes using microarray analysis of DNA methylation in samples from long-term follow-up patients with non-muscle invasive bladder cancer (NMIBC). Candidate methylation markers were selected from our previously published genome-wide methylation profiles. The clinical relevance of candidate methylation markers was determined by quantitative pyrosequencing analysis of 136 human bladder specimens (8 normal controls and 128 NMIBCs). The reversibility of DNA methylation was examined by 5-Aza-CdR treatment in human bladder cancer cell lines. The methylation patterns of candidate markers were significantly associated with aggressive clinicopathological features. In multivariate regression analysis, hypermethylation of radial spoke head 9 homolog (RSPH9) was an independent predictor of disease recurrence (hazard ratio, 3.02; P=0.001) and progression (hazard ratio, 8.25; P=0.028). The methylation level of RSPH9 decreased with 5-Aza-CdR treatment and progressively increased in its absence in bladder cancer cell lines. RSPH9 methylation is an independent prognostic indicator in NMIBC patients, and could be of value for the assessment of disease recurrence and progression and for clinical decision-making regarding treatment.
authors.affiliation: Advanced Technology Korea, Cheongju 28637, Republic of Korea.
authors.forename: Hyung-Yoon
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Yong-June
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Ji Sang
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Database/Bioinformatics Laboratory, Chungbuk National University, Cheongju 28644, Republic of Korea.
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Ryu
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C573132:RSPH9 protein, human; D001374:Azacitidine