Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer
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06/08/2014
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Resumo |
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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application/pdf |
Identificador | |
Publicador |
Impact Journals LLC |
Relação |
http://eprints.qut.edu.au/75577/1/White-Al_Habeeb_Linh_Olkhov-Mitsel.pdf http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2313 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. OICR/#10Nov-412 BILL&KATHLEEN TROOST/#701456 PCC/#2011-700 CIH/Post-doc fellowship White-Al Habeeb |
Direitos |
Copyright 2014 Impact Journals LLC 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. |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #060404 Epigenetics (incl. Genome Methylation and Epigenomics) #060408 Genomics #111203 Cancer Genetics #Prostate Cancer #Tumor Markers #biomarkers #epigenetics #DNA Methylation #expression array #DAC treatment #Demethylation agent treatment |
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Journal Article |