Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue

Milan S. Geybels, Shanshan Zhao, Chao Jen Wong, Marina Bibikova, Brandy Klotzle, Michael Wu, Elaine A. Ostrander, Jian Bing Fan, Ziding Feng, Janet L. Stanford

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCA) compared to adjacent benign tissue to identify differentially methylated CpG sites. Methods The study included paired PCA and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. Results In total, 2,040 differentially methylated CpG sites were identified in PCA versus adjacent benign tissue (Q-value<0.001), the majority of which were hypermethylated (n=1,946; 95%). DNA methylation profiles accurately distinguished between PCA and benign tissue samples. Twenty-seven top-ranked hypermethylated CpGs had a mean methylation difference of at least 40% between tissue types, which included 25 CpGs in 17 genes. Furthermore, for 10 genes over 50% of promoter region CpGs were hypermethylated in PCA versus benign tissue. The top-ranked differentially methylated genes included three genes that were associated with both promoter hypermethylation and reduced gene expression: SCGB3A1, HIF3A, and AOX1. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. Conclusions This study of PCA versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. Prostate 75:1941-1950, 2015.

Original languageEnglish (US)
Pages (from-to)1941-1950
Number of pages10
JournalProstate
Volume75
Issue number16
DOIs
StatePublished - Dec 1 2015

Keywords

  • DNA methylation
  • benign
  • mRNA expression
  • prostate cancer
  • tumor

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Geybels, M. S., Zhao, S., Wong, C. J., Bibikova, M., Klotzle, B., Wu, M., Ostrander, E. A., Fan, J. B., Feng, Z., & Stanford, J. L. (2015). Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue. Prostate, 75(16), 1941-1950. https://doi.org/10.1002/pros.23093