Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer
White-Al Habeeb, Nicole M.A., Linh, T. Ho, Olkhov-Mitsel, Ekaterina, Kron, Ken, Pethe, Vaijayanti, Lehman, Melanie, Jovanovic, Lidija, Fleshner, Neil, van der Kwast, Theodorus, Nelson, Colleen C., & Bapat, Bharati (2014) Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer. Oncotarget, 5(17), pp. 7858-7869.
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.
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|Item Type:||Journal Article|
|Keywords:||Prostate Cancer, Tumor Markers, biomarkers, epigenetics, DNA Methylation, expression array, DAC treatment, Demethylation agent treatment|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Epigenetics (incl. Genome Methylation and Epigenomics) (060404)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Genomics (060408)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2014 Impact Journals LLC|
|Copyright Statement:||This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Deposited On:||26 Aug 2014 22:22|
|Last Modified:||19 Aug 2015 00:10|
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