title: Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer.
abstract: Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2'-deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: White-Al Habeeb
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Linh T
authors.initials: LT
authors.lastname: Ho
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Department of Laboratory Medicine and Pathobiology, University of Toronto.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Olkhov-Mitsel
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Ken
authors.initials: K
authors.lastname: Kron
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital.
authors.forename: Vaijayanti
authors.initials: V
authors.lastname: Pethe
authors.affiliation: Australian Prostate Cancer Research Center, Queensland University of Technology, Brisbane, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lehman
authors.affiliation: Australian Prostate Cancer Research Center, Queensland University of Technology, Brisbane, Australia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Jovanovic
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network, Toronto, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto. Department of Pathology, University Health Network, Toronto, Canada.
authors.forename: Theodorus
authors.initials: T
authors.lastname: van der Kwast
authors.affiliation: Australian Prostate Cancer Research Center, Queensland University of Technology, Brisbane, Australia. .
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Department of Laboratory Medicine and Pathobiology, University of Toronto. Department of Pathology, University Health Network, Toronto, Canada.
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor