Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [ATAC-seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201336 | GEO | 2022/04/28
REPOSITORIES: GEO
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Project description:To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from polyps, normal tissues, and CRCs collected from patients with or without germline APC mutations. We find that a large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC.
2022-04-28 | GSE201348 | GEO
Project description:In this study we compared gene expression of precancerous SSA/Ps and benign MVHPs with particular focus on genes involved in colorectal cancer. We also identify genes whose expression can be used to differentiate SSA/Ps and MVHPs. These results provide insight into the development of SSA/Ps and illustrates differences between these related colonic polyps. Total RNA from 6 samples of normal colon, 6 microvesicular hyperplastic polyps, and 6 sessile serrated adenomas/polyps were compared
2013-07-09 | E-GEOD-43841 | biostudies-arrayexpress
Project description:Sessile serrated adenomas are now recognized as precursor lesions of a substantial subset of colorectal cancers arising via a so-called “serrated pathway”. However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas, hyperplastic polyps and tubular adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using QRT-PCR on Cathepsin E demonstrated a significantly (p< 0.05) higher expression in sessile serrated adenomas as compared to both other polyp types. Trefoil Factor 1, showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps, and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas while staining in tubular adenomas and hyperplastic polyps was weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (P<0.05). This study demonstrates CTSE and TFF1 over-expression in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. Keywords: colonic polyp tissue comparison, linear modelling, SSA
2008-08-27 | GSE12514 | GEO
Project description:FAP is an autosomal-dominant inherited disease caused by germline mutations in the APC gene 1. Two major FAP phenotypes, CFAP and AFAP, can be distinguished based on polyp numbers and age of onset. CFAP is characterized by the presence of hundreds to thousands of polyps. About half of these patients develop adenomas by age 15, and 95% develop adenomas by age 35. AFAP patients exhibit a milder phenotype than CFAP patients; AFAP is characterized by fewer polyps, later adenoma onset, and lower CRC risk. We used microarrays to analyze chromosome abberation of organids established from FAP patients.
2019-12-31 | GSE109813 | GEO
Project description:FAP is an autosomal-dominant inherited disease caused by germline mutations in the APC gene 1. Two major FAP phenotypes, CFAP and AFAP, can be distinguished based on polyp numbers and age of onset. CFAP is characterized by the presence of hundreds to thousands of polyps. About half of these patients develop adenomas by age 15, and 95% develop adenomas by age 35. AFAP patients exhibit a milder phenotype than CFAP patients; AFAP is characterized by fewer polyps, later adenoma onset, and lower CRC risk. We used microarrays to analyze the expression profiles of organoids established from three CFAP and two AFAP patients.
2019-12-31 | GSE109812 | GEO
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP. Twelve asthmatic chronic rhinosinusitis (aCRS) subjects (11 with nasal polyps; aCRSwNP) provided inflamed nasosinus mucosa (11 samples) and adjacent polyp (10 samples) or a small mixed mucosa and polyp specimen (1 sample) (thus, 22 samples overall). Inflamed mucosa or polyp was from the middle meatus or anterior ethmoid cavity. As control samples, nasosinus tissue was collected from the inferior turbinate or uncinate process from normal or rhinitis subjects without nasal polyps (n=17); 4 had physician-diagnosed allergic rhinitis (AR), 2 had suspected AR, 1 had suspected vasomotor rhinitis, and 10 had no signs of nasosinus disease, allergy, or atopy. All 4 AR subjects chose to donate tissue outside of their known allergy season(s).
2010-08-12 | E-GEOD-23552 | biostudies-arrayexpress
Project description:Genetic and epigenetic alterations are a fundamental aspect of colorectal cancer formation. There is considerable heterogeneity between colorectal cancers regarding the mutations and methylated genes they carry, and this heterogeneity may arise early in the polyp-cancer sequence. However, our understanding of the epigenetic alterations and gene mutations in colon adenomas and their relation to colorectal cancer is incomplete. Thus, we have assessed the methylome in normal colon mucosa, tubular adenomas, and colorectal adenocarcinomas and have determined the relationship of these findings between adenomas and cancer in the colon. Genome-wide alterations in DNA methylation were found in the normal colon mucosa adjacent to colorectal cancer, tubular adenomas, and colorectal cancer. Three subgroups of CRCs and two subgroups of adenomas were identified on the basis of their DNA methylation patterns. The adenomas separated into a high-frequency methylation class (Adenoma-H) and a low-frequency methylation class. The adenoma-H polyps have a methylated DNA signature similar to non-CIMP CRCs, whereas those of the Adenoma-L class have a similar methylation pattern to normal colon mucosa. The CpGs that account for these signatures are located in intragenic/intergenic regions, which suggests that these two groups of adenomas arise from different stem cell populations.
2014-09-08 | GSE48684 | GEO
Project description:Genetic and epigenetic alterations are a fundamental aspect of colorectal cancer formation. There is considerable heterogeneity between colorectal cancers regarding the mutations and methylated genes they carry, and this heterogeneity may arise early in the polyp-cancer sequence. However, our understanding of the epigenetic alterations and gene mutations in colon adenomas and their relation to colorectal cancer is incomplete. Thus, we have assessed the methylome in normal colon mucosa, tubular adenomas, and colorectal adenocarcinomas and have determined the relationship of these findings between adenomas and cancer in the colon. Genome-wide alterations in DNA methylation were found in the normal colon mucosa adjacent to colorectal cancer, tubular adenomas, and colorectal cancer. Three subgroups of CRCs and two subgroups of adenomas were identified on the basis of their DNA methylation patterns. The adenomas separated into a high-frequency methylation class (Adenoma-H) and a low-frequency methylation class. The adenoma-H polyps have a methylated DNA signature similar to non-CIMP CRCs, whereas those of the Adenoma-L class have a similar methylation pattern to normal colon mucosa. The CpGs that account for these signatures are located in intragenic/intergenic regions, which suggests that these two groups of adenomas arise from different stem cell populations. We conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in 41 normal colon samples, 42 colon adenomas, and 64 colorectal cancers. Supplementary file 'GSE48684_Matrix_signal_intensities_1.txt.gz': includes the unmethylated and methylated signal intensities from Samples GSM1183439-GSM1183561. Supplementary file 'GSE48684_Matrix_signal_intensities_2.txt.gz': includes the unmethylated and methylated signal intensities from Samples GSM1235135-GSM1235158.
2014-09-08 | E-GEOD-48684 | biostudies-arrayexpress
Project description:Background: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathological, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. Results: To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues, but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent over- and underexpression of 78 known components of this signaling cascade. Conclusions: Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis. Experiment Overall Design: Pedunculated, sporadic colorectal polyps and corresponding normal mucosa were obtained during colonoscopies. The tissues were collected prospectively with informed patient consent and the approval of the local Human Research Ethics Committee.
2008-06-16 | E-GEOD-8671 | biostudies-arrayexpress
Project description:Sessile serrated adenomas are now recognized as precursor lesions of a substantial subset of colorectal cancers arising via a so-called “serrated pathway”. However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas, hyperplastic polyps and tubular adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using QRT-PCR on Cathepsin E demonstrated a significantly (p< 0.05) higher expression in sessile serrated adenomas as compared to both other polyp types. Trefoil Factor 1, showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps, and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas while staining in tubular adenomas and hyperplastic polyps was weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (P<0.05). This study demonstrates CTSE and TFF1 over-expression in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. Keywords: colonic polyp tissue comparison, linear modelling, SSA Microarray analysis was performed on 13 SSAs and 11 TAs. SSAs were from 4 males and 9 females (mean age of 75) and TAs were from 5 males and 6 females (mean age of 72). Samples were directly hybridised to each other (SSA versus TA) or to a pooled normal control (SSA versus control). A linear model (Smyth 2004) was fitted to the data bringing together the three contrasts: SSA versus control, TA versus control and SSA versus TA. Human OligoLibrary (Compugen Human Oligo Library (v1) containing 18861 60-mer oligonucleotides, representing approximately 16,000 unique genes) by the Adelaide Microarray Centre (Australia) was used. Slides were scanned using a GenePix 3000B scanner (Axon Instruments, Sunnydale, CA), and the Spot package (CSIRO, Australia) was used to identify spots and estimate fore- and background intensities (using a morphological opening background estimator) (Yang, Buckley et al. 2001; Ritchie 2004). Data analysis was performed in R (www.r-project.org) using the Limma package of Bioconductor (Gentleman, Carey et al. 2004; Smyth 2004). Loess print tip method was used to correct for dye-bias and intensity within each group of adjacent spots printed by one pin (Yang, Dudoit et al. 2002). Linear modelling was performed with the Limma package of Bioconductor (Smyth 2004).
2008-08-26 | E-GEOD-12514 | biostudies-arrayexpress