title: Global methylation profiling for risk prediction of prostate cancer.
abstract: OBJECTIVE
  The aim of this study was to investigate the promoter hypermethylation as diagnostic markers to detect malignant prostate cells and as prognostic markers to predict the clinical recurrence of prostate cancer.
  
  
  METHODS
  DNA was isolated from prostate cancer and normal adjacent tissues. After bisulfite conversion, methylation of 14,495 genes was evaluated using the Methylation27 microarrays in 238 prostate tissues. We analyzed methylation profiles in four different groups: (i) tumor (n = 198) versus matched normal tissues (n = 40), (ii) recurrence (n = 123) versus nonrecurrence (n = 75), (iii) clinical recurrence (n = 80) versus biochemical recurrence (n = 43), and (iv) systemic recurrence (n = 36) versus local recurrence (n = 44). Group 1, 2, 3, and 4 genes signifying biomarkers for diagnosis, prediction of recurrence, clinical recurrence, and systemic progression were determined. Univariate and multivariate analyses were conducted to predict risk of recurrence. We validated the methylation of genes in 20 independent tissues representing each group by pyrosequencing.
  
  
  RESULTS
  Microarray analysis revealed significant methylation of genes in four different groups of prostate cancer tissues. The sensitivity and specificity of methylation for 25 genes from 1, 2, and 4 groups and 7 from group 3 were shown. Validation of genes by pyrosequencing from group 1 (GSTP1, HIF3A, HAAO, and RARβ), group 2 (CRIP1, FLNC, RASGRF2, RUNX3, and HS3ST2), group 3 (PHLDA3, RASGRF2, and TNFRSF10D), and group 4 (BCL11B, POU3F3, and RASGRF2) confirmed the microarray results.
  
  
  CONCLUSIONS
  Our study provides a global assessment of DNA methylation in prostate cancer and identifies the significance of genes as diagnostic and progression biomarkers of prostate cancer.
authors.affiliation: Department of Urology and Laboratory Medicine and Pathology, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Saswati
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.forename: Charles Y F
authors.initials: CY
authors.lastname: Young
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: George G
authors.initials: GG
authors.lastname: Klee
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Tindall
authors.forename: Krishna Vanaja
authors.initials: KV
authors.lastname: Donkena
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm