945 Infection of H. pylori Is Associated With Promoter Methylation of a Putative STAT3 Targeted microRNA, miR-193a in Gastric Cancer

Abstract

G A A b st ra ct s these findings. The present study seeks to identify biologic differences in methylation among these three racial/ethnic groups. Methods: We performed an array-based study of aberrantly methylated loci in CRCs and neighboring normal tissue using HumanMethylation450 arrays (Illumina). Paired FFPE CRC samples (n=42) and neighboring normal tissue were obtained from the case records of the pathology department at the University of Miami Hospital and Sylvester Comprehensive Cancer Center (Miami, FL). Samples were segregated into racial/ ethnic categories of black, Hispanic, and NHW and matched for age and stage. DNA was extracted from 10 micron thick colon tissue resection samples, with target enrichment, sequencing, and automated analysis performed using manufacturer protocols for the HumanMethylation450 array. Methylome-wide tumor vs. normal differential methylation was performed on each sample pair. Significantly methylated loci (FDRp<0.05) in ≥90% of samples in each ethnic group were prioritized, and overlap was sought between ethnic groups. Pathway and gene ontology analyses were conducted assuming a hypergeometric model with the MetaCore software. Results: 13 BNH, 18 Hispanic, and 11 NHW matched pairs of normal colon and CRC were included. 10 differentially methylated regions (DMRs) were significant both within and across all ethnic groups. All DMRs were hypermethylated, previously shown to be hypermethylated in cell lines, and several (e.g., MDFI, RYR2, OPLAH) were identified as top hits from published independent genome-wide methylation analyses. 73, 329, and 2379 DMRs were unique to Black, Hispanic, and NHW groups, respectively. The CpG sites that were differentially methylated (both hypoand hyper-methylation) were localized to intragenic and intergenic regions. Pathway analyses revealed unique signatures of methylation targets between ethnic groups. In contrast to Black and Hispanic datasets, the colorectal cancer (general schema) pathway was significant (FDRp<0.05) only in NHW. Conclusions: These results confirm common CRC methylation signals independent of racial/ ethnic labels and also reveal potential racialand ethnic-specific CRC methylation signatures. Clarification of these findings may contribute to the understanding of the phenotypic differences observed in patients with CRC among these groups.