Identifying Epigenomic Biomarkers for Anticancer Drug Responses by Integrating Gene Expression and DNA Methylation Profiles

• Activity Number: 368
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhibao Mi*+ and Kui Shen and Nan Song
• Companies: VA and Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh and the NSABP Foundation, Inc.
• Keywords: Epigenomic Biomarkers ; Drug Responses ; Integrated analysis ; Next Generation Sequencing ; DNA Methylation ; RNA-seq

Abstract

The rapidly advancing next generation sequencing technology has been applied to biomedical research in a variety of contexts, including accurately measuring mRNA abundance by RNA-seq and detecting DNA methylation status by bisulfite-sequencing at the level of single-base resolution. Integrated analysis by combining DNA methylation patterns and gene expression profiling to facilitate understanding of epigenomic mechanisms is analytically challenging. We propose an analysis pipeline to integrate DNA methylation and gene expression profiles to identify epigenomic biomarkers for anticancer drug responses. The profile of DNA methylation and mRNA expression for seven breast cancer cell lines is used as an example to study the epigenomic regulation of resistance to antitumor antibiotics (e.g. epirubicin). Eleven differentially expressed genes regulated by CpG islands were identified and a pathway enrichment analysis indicates that these genes are related to DNA replication, repair and drug metabolism. These genes are further validated by publically available clinical trial data and could be potential novel biomarkers for breast cancer treatment.