Racial Disparities in Epigenetic Aging of the Right versus the Left Colon
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151732 | GEO | 2020/10/16
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:Background: An increasing body of evidence has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) consume greater quantities of fructose and are more likely to develop right-side colon cancer than European Americans. Objective: We examined the hypothesis that fructose consumption leads to genomic differences associated with CRC tumor biology. Methods: DNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit (GSE151732). Right and left colon differentially methylated regions (DMRs) were identified using DMRcate through analysis of fructose consumption in normal AA colon biopsies (n=79) undergoing screening colonoscopy. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Right colon organoids derived from AA normal colon tissues were exposed to 4.4mM of fructose for 72 hours. Fructose-associated differentially expressed genes (DEGs) were identified using DESeq2. This package was also used to identify DEGs in CRC tumors from TCGA-COAD. Results: We identified 4,263 right colon fructose-associated DMRs (FDR<0.05). In contrast, only 24 DMRs survived multiple testing corrections (FDR<0.05) in matched, left colon. Almost 50% of right colon fructose-associated DMRs overlapped regions implicated in CRC in at least one of three datasets. A highly significant enrichment was also observed between genes corresponding to right colon fructose-associated DMRs and DEGs associated with fructose exposure in AA right colon organoids (P=3.28E-30). Further, overlapping and significant enrichments for a number of fatty acid metabolism, glycolysis and cell proliferation pathways were also found. By further examining the overlap of genes within these pathways that were also differentially expressed in TCGA-COAD, our analysis reveals potential role for PFKP and ANKRD23 in fructose-mediated CRC risk. Conclusions: Our data support that dietary fructose exerts a greater CRC risk-related effect in right than left colon among AAs, alluding to its potential role in contributing to racial disparities in CRC.
2025-03-15 | GSE261717 | GEO
Project description:Colorectal cancer often arises from adenomatous polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Prediciting which progress to cancer and which remain benign is difficult. We developed a long-lived murine model of colorectal cancer with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk stratification of colonic tumors. Long-lived Apcin/+ mice were treated with 4% dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy, and pathology was determined. Serial biopsies of tumors were obtained for immunohistochemistry and gene expression profiling by microarray analysis with Affymetrix Whole Genome array. Tumors (n=424) grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated dynamic growth patterns with higher rates of growth and resolution, while more established tumors tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Differentially expressed genes between adenomas and intramucosal carcinomas were identified. We did not identify differentially expressed genes between early and late biopsies from the same tumor. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to colorectal cancer. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progress to colorectal cancer and potentially guide prevention strategies. F1 (SWR x C57BL/6) Apcin/+ mice who had been given two treatments of 4% dextran sodium sulfate in drinking water at weaning underwent colonoscopy around 80 days of age. Those with distal colonic tumors amenable to biopsy had two biopsies taken at that time. Tumors were monitored by colonoscopy every 14 days. Every 28 days, two additional biopsies were taken of each tumor. This protocol was repeated until mice were moribund. Six tumors were removed after sacrifice. The earliest and latest biopsies of each tumor were selected for RNA extraction and Affymetrix hybridization.
2014-05-03 | E-GEOD-46626 | biostudies-arrayexpress
Project description:Genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. Here, we comprehensively map eQTLs in the human colon, assess their relevance for GWAS of colonic diseases and provide functional characterization. Subjects included 40 healthy African American individuals who had undergone colonoscopy at the University of Illinois Chicago for screening purposes. Distal colonic biopsies were obtained in all subjects at 20 cm from the anal verge at the recto-sigmoid junction and were immediately dispensed in RNAlater. Total mRNA was extracted from manually ground tissue with the Promega Maxwell 16 Tissue LEV Total RNA Purification Kit for automated purification on the Maxwell 16 Instrument and mRNA analysis was performed on Illumina HumanHT-12v4 Expression BeadChip arrays. Genomic DNA was obtained from whole-blood samples from the same individuals and genotyped using the Affymetrix Axiom Genome-wide Pan-African array. Cis- and trans-eQTL analyses were performed on the dataset of 8.4 million imputed SNPs and 16,252 expression probes corresponding to 12,363 unique autosomal genes in 40 subjects. Associations between SNPs and gene expression levels were examined with Matrix eQTL using linear regression. False discovery rate calculations were performed separately for cis- and trans-eQTLs.
2014-04-15 | E-GEOD-56789 | biostudies-arrayexpress
Project description:Infliximab, an anti-TNF-alpha monoclonal antibody, is an effective treatment for ulcerative colitis (UC) with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-TNF-alpha is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in UC. Keywords: drug response Twenty-four patients with active UC, refractory to corticosteroids and/or immunosuppression, underwent colonoscopy with biopsies from diseased colon within a week prior to the first intravenous infusion of 5 mg infliximab per kg body weight. Response to infliximab was defined as endoscopic and histologic healing at 4-6 weeks after first infliximab treatment. Six control patients with normal colonoscopy were included. Total RNA was isolated from colonic mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.
2010-01-06 | E-GEOD-14580 | biostudies-arrayexpress
Project description:Racial Disparities in Epigenetic Aging of the Right versus the Left Colon
| PRJNA637075 | ENA
Project description:Colorectal cancer often arises from adenomatous polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Prediciting which progress to cancer and which remain benign is difficult. We developed a long-lived murine model of colorectal cancer with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk stratification of colonic tumors. Long-lived Apc^Min/+ mice were treated with 4% dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy, and pathology was determined. Serial biopsies of tumors were obtained for immunohistochemistry and gene expression profiling by microarray analysis with Affymetrix Whole Genome array. Tumors (n=424) grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated dynamic growth patterns with higher rates of growth and resolution, while more established tumors tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Differentially expressed genes between adenomas and intramucosal carcinomas were identified. We did not identify differentially expressed genes between early and late biopsies from the same tumor. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to colorectal cancer. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progress to colorectal cancer and potentially guide prevention strategies.
2014-05-03 | GSE46626 | GEO
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal polyps are recognised pre-cursors of CRC, however hyperplastic polyps lack malignant potential. The purpose of this study was to identify differences in gene expression between normal colonic mucosa, hyperplastic and adenomatous polyps from disease-free individuals. By comparing polyps believed to have malignant potential (adenomatous polyps) with hyperplastic polyps it is hoped that new insights into colorectal carcinogenesis can be achieved. 24 colonic samples comprising 8 normal colonic mucosa, 8 hyperplastic polyps and 8 adenomatous polyps.
2012-08-25 | E-GEOD-40362 | biostudies-arrayexpress
Project description:Colonic aspirates were collected at diagnostic colonoscopy from inflammatory bowel disease (IBD) and control, treatment-naive children. The colonic mucosal-luminal interface (MLI) proteomes were analyzed for 18 control and 42 IBD patients by liquid-chromatography mass spectrometry.
2018-03-19 | PXD006383 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE25275: Gene expression patterns of biopsies from a colonoscopy taken in 2007 of an ulcerative colitis patient infected with Trichuris trichiura GSE25276: Gene expression patterns of biopsies from a colonoscopy taken in 2008 of an ulcerative colitis patient infected with Trichuris trichiura GSE25277: Gene expression patterns of biopsies from a colonoscopy taken in 2009 of an ulcerative colitis patient infected with Trichuris trichiura Refer to individual Series
2010-11-20 | E-GEOD-25510 | biostudies-arrayexpress
Project description:The challenge of preventing colorectal cancer (CRC) is the early identification of individuals whose apparently normal colorectal mucosa will develop cancer, because of inherited trait or environmental exposure. We sought to use genome-wide expression profiling of endoscopic biopsies to detect a signature of propensity for cancer. We performed oligonucleotide microarray analysis of normal appearing mucosa of the following cases: healthy individuals (NOR), disease-free carriers predisposed to HNPCC (hereditary non-polyposis CRC), disease-free patients who underwent curative large bowel resection for CRC 1 to 15 years earlier and patients with CRC (MCRC) (GSE23011). As test set we run on affymetrix arrays an independent set of mucosal biopsies of MCRC and NOR samples. This profiling is based on the analysis of 5 patients who underwent curative large bowel resection for CRC from 1 to 15 years before (MCRC samples), and 12 endoscopy-negative, asymptomatic individuals (NOR samples)
2013-11-30 | E-GEOD-23194 | biostudies-arrayexpress