Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA549184 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome wide DNA methylation profiling of normal colon samples. The Illumina Infinium HumanMethylation450 and EPIC Beadchip arrays were used to obtain DNA methylation profiles across approximately 450,000 and 850,000 CpGs. Samples were from nomal colons of 334 subjects with low, medium or high CRC risk according to their personal adenoma or cancer history.
2019-12-31 | GSE132804 | GEO
Project description: Not available
| S-EPMC6942339 | biostudies-literature
Project description:To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers' putatively targeted genes, we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function Two biological replicates of HCT116 were compared to the data of two normal colon samples already deposited in GEO (GSM1010974 and GSM1010942).
2014-10-01 | E-GEOD-52429 | biostudies-arrayexpress
Project description:Atlas of the aging mouse colon
| PRJNA707433 | ENA
Project description:Importance: Neighborhood socioeconomic status has been associated with increased colorectal cancer (CRC) risk, particularly among different racial groups, yet the biological mechanisms underlying this association remain unclear. Objective: To investigate whether neighborhood deprivation, as assessed by Neighborhood Deprivation Index (NDI), is associated with differential gene expression in normal colorectal biopsies; to explore molecular links to CRC risk and to identify potential chemoprevention targets. Design: A cross-sectional study involving transcriptomic analysis of normal colorectal tissues and meta-analysis of gene expression data between African Americans (AA) and European Americans (EA), and an experimental study exposing colon organoids derived from healthy colon biopsies to metformin. Setting: Participants were enrolled in the Cleveland Colon Screening and Risk Factors Study (2012-2018) in metropolitan Cleveland, Ohio. Organoids were derived from colon biopsies of patients undergoing colonoscopy in Charlottesville, Virginia. Participants: Normal colorectal biopsies from AA (n = 34) and EA (n = 23) adults undergoing colonoscopy were analyzed. Colon organoids were derived from AA (n = 4) and EA (n = 6) individuals. RNA-seq data was generated from each participant. Main Outcome(s) and Measures: Differentially expressed genes (DEGs) associated with NDI in normal colorectal biopsies and overlap with DEGs identified in CRC tumor tissues; and association of metformin on NDI-associated, CRC risk gene expression. Results: A total of 237 DEGs were found to be commonly associated with NDI across individual-matched biopsy triplets (right and left colon, and rectum) in both racial groups. Cellular metabolism pathways were amongst the most significantly enriched within identified DEGs. Of the 237 NDI associated DEGs, 82 overlapped with CRC tumor DEGs from a publicly available dataset (TCGA-COADREAD; P=2.21×10⁻⁵; OR=1.83), and nine were prioritized as therapeutic targets, including MYC overexpression (BH=2.48E-12). Metformin exposure in colon organoids also altered the expression of 28 of these genes, with ~79% showing opposite direction, including reduced MYC expression (BH=0.095). Conclusion and Relevance: NDI is associated with CRC-related transcriptional differences. These findings suggest potential molecular mechanisms linking neighborhood deprivation to CRC risk. The observed reversal of gene expression by metformin suggests a potential role for metformin in reducing CRC risk in high NDI-populations, who face greater than average risk of developing CRC.
2026-04-10 | GSE319878 | GEO
Project description:Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis
| PRJNA777445 | ENA
Project description:To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers' putatively targeted genes, we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function
2014-10-01 | GSE52429 | GEO
Project description:Colon cancer is one of the leading causes of death within the western world and is linked to the aging of the colon. The disease presents differently between men and women, developing in different parts of the colon and often with a different morphology. The colonic epithelium is a rapidly renewing tissue, tasked with absorption of water and nutrients, interacting with a wide array of intestinal microbes. The gut-associated lymphoid tissue houses the majority of all immune cells. These immune cells interact with and help regulate the activity of epithelial cells. However, not much is known whether compartment-specific changes occur during aging and how said changes could impact the epithelium. Here we show that both epithelial and immune cells differ significantly between colonic compartments and experience age-related changes, with the possible causal interactions. We found a shift in the absorptive-secretory cell balance, the decrease in colonocytes possibly linked to age-associated malabsorption and intestinal disturbances. We demonstrate marked changes in the aging of the immune cells with regard to populations and interactions with epithelial cells, linking aged immune cell produced cytokines (Ifn-γ, Il1B) and the aging of colonic epithelium, which lines up with observations of inflammation causing or exacerbating age-associated gut disfunctions, such as colon cancer. Our results provide new insights into the normal and age-associated states of the colon. We anticipate our work will provide a foundation for further inquiry not only into diseases of the colon (even outside the realm of aging research) but developmental research as well.
2022-03-31 | GSE168448 | GEO
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:IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2
| PRJNA750059 | ENA