The genomic landscape of serrated lesion of the colorectum
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PROVIDER: EGAS00001005648 | EGA |
REPOSITORIES: EGA
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Project description:RNA sequencing analysis of small RNA expression in sessile serrated adenoma/polyps, hyperplastic polyps, adenomatous polyps, uninvolved colon and control colon
2018-10-18 | GSE118504 | GEO
Project description:Consensus molecular subtyping in adenomatous and serrated polyps
2018-12-19 | GSE108317 | GEO
Project description:This study was conducted to explore the serum methylome of precancerous lesions belonging to the serrated pathway of colorectal carcinogenesis in a prospective multicentre cohort. Individuals were grouped into five main categories: (i) serrated adenocarcinoma (SAC), (ii) high-risk serrated polyps (HR-SP) comprising traditional serrated adenomas (TSA), sessile serrated lesions (SSL), and serrated polyps (SP) with dysplasia or ≥ 10 mm; (iii) high-risk hyperplastic polyps (HR-HP), defined as HP ≥ 10 mm; (iv) low-risk serrated lesions (LR-SL) including SP without dysplasia < 10 mm and HP < 10 mm; and (v) healthy individuals with no colorectal findings (NCF). First, epigenome-wide methylation levels were quantified in pooled cfDNA samples to characterize the differential methylation profile between no serrated neoplasia (NSN: NCF and LR-SL) and high-risk serrated lesions (HR-SL: HR-HP and HR-SP); concordance with tissue methylation levels was assessed using external datasets. Then, the pathway-specific cfDNA methylation signature was evaluated together with cfDNA pools from the conventional CRC pathway. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.
2024-03-01 | GSE199173 | GEO
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: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
Project description:Adenomatous polyps adjacent to colorectal cancer (CRC) were found to exhibit two distinct microRNAs (miRs) patterns from normal mucosa to low- and separately, to high-grade dysplasia; presence in screen-detected adenoma of non-cancer patients is unknown. Global miR expression was performed on biopsies obtained from 109 healthy patients undergoing screening/surveillance colonoscopy. Included were normal mucosa (NM); hyperplastic polyp (HP); tubular adenoma (TA), tubulovillous adenoma, with or without, high-grade dysplasia (TVHG) and serrated-polyps; sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA). Logistic regression was used to model miRs predictive of histology and CRC risk. We identified 99 miRs that differed across five histologic groups (FDR=0.05) and that accurately separated on histology (Concordance Index (CI)=0.96). In HPNM, miRs-145, -143, -107a, -23b, and -24 were upregulated whereas miRs-663, -1268, -320b, -1275, and -671 where overexpressed in TVHGs (FDR P<0 .05). The expression of miR-145 and -30a showed high accuracy to separate low from high-risk polyps independent of serrated status (CI= 97.1%; AUC 93.4%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs and miR-335 discriminated between non-serrated and serrated histology. Histologically advanced polyps from non-cancer patients share miR alterations with those reported for CRC and high-grade adenoma adjacent to tumor including downregulation of immune regulatory miRs-125 and -199a in TSAs; polyp that frequently present with in situ carcinoma. These data extend evidence that miR patterns of high-risk adenoma are detectable in subset of screen-detected adenoma for which measurement may be useful in in adenoma risk stratification.
2015-09-29 | GSE73487 | GEO
Project description:Background: The change of cellular energy metabolism in colorectal carcinogenesis is poorly understood. It is widely accepted tht most, if not all, colorectal cancers (CRCs) arise from adenomatous polyps (APs). Our aim was to characterize the mitochondrial and bioenergetic alternations in the adenoma-carcinoma sequence. Results: Two glycolysis-related genes, aldolase B (ALDOB) and solute carrier family 16 member 4 (SLC16A4), were upregulated in polyps. This result was further confirmed by the real-time PCR analysis showing that the both ALDOB and SLC16A4 mRNA expressions were higher in the polyps with villous component compared with their adjacent normal mucosa.
2017-05-23 | GSE81804 | GEO
Project description:Colorectal cancer can be divided into four consensus molecular subtypes, which might associate with distinct precursor lesions. The aim of this study was to determine the subtype affiliation of two types of colorectal adenomas: tubular adenomas (TAs) and sessile serrated adenomas (SSAs) and to determine the activity of TGFβ signaling and the role of this cytokine in subtype affiliation. Adenoma samples were collected in the Academic Medical Center (AMC), Amsterdam, The Netherlands. Tubular adenomas (TAs) were obtained from familial adenomatous polyposis (FAP) patients and sessile serrated adenomas (SSAs) were collected from serrated polyposis syndrome (SPS) patients. Gene expression was analyzed for 7 sessile serrated adenomas (SSA) and 9 tubular adenomas (TA).
2016-06-01 | E-GEOD-79460 | biostudies-arrayexpress
Project description:The preferential localization of some neoplasms, such as serrated polyps, in specific areas of the intestine suggests that non-genetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine, but develop serrated polyps only in the cecum. Here we show that a host-specific microbiome was associated with serrated polyps, and that alterations of the microbiota induced by antibiotic treatment or by embryo-transfer rederivation markedly inhibited the formation of serrated polyps in the cecum. Mechanistically, development of serrated polyps was associated with a local decrease in epithelial barrier-function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1. Increased number of neutrophils were found within the serrated polyps, and their depletion significantly reduced polyp growth. Together these results indicate that non-genetic factors contribute to the development of serrated polyps and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.
2014-02-12 | GSE47735 | GEO
Project description:The preferential localization of some neoplasms, such as serrated polyps, in specific areas of the intestine suggests that non-genetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine, but develop serrated polyps only in the cecum. Here we show that a host-specific microbiome was associated with serrated polyps, and that alterations of the microbiota induced by antibiotic treatment or by embryo-transfer rederivation markedly inhibited the formation of serrated polyps in the cecum. Mechanistically, development of serrated polyps was associated with a local decrease in epithelial barrier-function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1. Increased number of neutrophils were found within the serrated polyps, and their depletion significantly reduced polyp growth. Together these results indicate that non-genetic factors contribute to the development of serrated polyps and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.
2014-02-12 | GSE47734 | GEO