A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis

Abstract

The cause of inflammatory bowel disease (IBD) is still unknown, but there is growing evidence that environmental factors such as epigenetic changes can contribute to the disease etiology. The aim of this study was to identify newly hypermethylated genes in ulcerative colitis (UC) using a genome-wide DNA methylation approach. Using an Infinium HumanMethylation450 BeadChip array, we screened the DNA methylation changes in three normal colon controls and eight UC patients. Using these methylation profiles, 48 probes associated with CpG promoter methylation showed differential hypermethylation between UC patients and normal controls. Technical validations for methylation analyses in a larger series of UC patients (n = 79) were performed by methylation-specific PCR (MSP) and bisulfite sequencing analysis. We finally found that three genes (FAM217B, KIAA1614 and RIBC2) that were significantly elevating the promoter methylation levels in UC compared to normal controls. Interestingly, we confirmed that three genes were transcriptionally silenced in UC patient samples by qRT-PCR, suggesting that their silencing is correlated with the promoter hypermethylation. Pathway analyses were performed using GO and KEGG databases with differentially hypermethylated genes in UC. Our results highlight that aberrant hypermethylation was identified in UC patients which can be a potential biomarker for detecting UC. Moreover, pathway-enriched hypermethylated genes are possibly implicating important cellular function in the pathogenesis of UC. Overall, this study describes a newly hypermethylated gene panel in UC patients and provides new clinical information that can be used for the diagnosis and therapeutic treatment of IBD.

Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma

“…To ensure consistency of data processing, we only compared our samples with publically accessible samples with raw idat files. GSE68060, GSE68838, GSE77954, GSE77965, GSE81211, GSE101764, GSE107352, and GSE75546 were collected from GEO while E-MTAB-6450 was collected from ArrayExpress [43][44][45][46][47][48] (Additional file 1: Table S6). Some cell line samples and metastatic cancer samples were removed upon further study.…”

Hypermethylated promoters of tumor suppressor genes were identified in Crohn’s disease patients

“…18 Patients with IBD can be grouped as lifetime risk (2-to 3-fold greater) of developing CRC, and the most important risk factors for colitis-associated cancer are duration, severity and extent of the IBD. 13,14 There is a growing body of evidence suggesting that inflammation is the critical cause of many cancers, and colitis-associated cancer serves as a great model system to study the general principles understanding for the etiology of inflammation-associated cancer. 19 Prevalent evidence supports the theory that IBD is caused by a complex interplay between the predispositions of multiple genes and abnormal interactions with environmental factors.…”

Systems biology in inflammatory bowel diseases: on the way to precision medicine

“…The same investigators also identified 8 differentially methylated regions (DMRs) close to 8 different genes, and some of these genes were associated with immune-related pathways [71]. Regarding UC patients, Kang et al also found differentially methylated patterns in UC patients with 3 genes, FAM217B, KIAA1614 and RIBC2, being hypermethylated; thus, this might be a tool for distinguishing UC patients from healthy individuals [72]. In a recent study, mucosal biopsies taken from UC patients showed different methylation patterns from those of healthy individuals; UC patients showed hyper-methylation or hypo-methylation in genes involved in homeostasis and defense, or in immune response pathways, respectively [73].…”