Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns

BMC Cancer

Research Article

James D. Brooks¹  Zulfiqar G. Gulzar²  Brittany N. Lasseigne³  Devin M. Absher³  Sara J. Cooper³  Richard M. Myers³  Brian S. Roberts³  Ryne C. Ramaker⁴  Todd C. Burwell⁵  Nicholas S. Davis⁶  Marie K. Kirby⁷  David S. Gunther⁸ 

[1] Department of Urology, Stanford University Medical Center, Room S287, 300 Pasteur Drive, 94305-5118, Stanford, CA, USA;Department of Urology, Stanford University Medical Center, Room S287, 300 Pasteur Drive, 94305-5118, Stanford, CA, USA;Present Address: NuGEN technologies, 201 Industrial Rd #310, 94070, San Carlos, CA, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;Department of Genetics, Kaul Human Genetics Building, Suite 230, 720 20th Street South, 35294, Birmingham, AL, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;Present Address: Boeing Co., 499 Boeing Blvd, SW, 35824, Huntsville, AL, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;Present Address: Duke University, 101 Science Drive, 27708, Durham, NC, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;Present Address: TRM Oncology, 5901-C Peachtree Dunwoody Rd, Suite 200, 30328, Atlanta, GA, USA;HudsonAlpha Institute for Biotechnology, 601 Genome Way, 35806, Huntsville, AL, USA;Present Address: University of Southern California, University Park, 90089, Los Angeles, CA, USA;

关键词: DNA methylation;    Prostate cancer;    EZH2;    Biomarker;    Diagnostic;   

DOI  :  10.1186/s12885-017-3252-2

 received in 2016-01-30, accepted in 2017-04-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCurrent diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer.MethodsWe measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models.ResultsWe identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues.ConclusionsDNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

【 授权许可】

CC BY   
© The Author(s). 2017