Specific serum methylome of the serrated pathway of colorectal carcinogenesis
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ABSTRACT:
PROVIDER: PRJNA818691 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Despite recent different molecular classifications for colorectal cancer (CRC) have been proposed, CRCs are currently diagnosed based their histology [Hamilton] and just a few biomarkers are used to determine the most suitable treatment. It is for this reason important to correlate molecular profiling with histological features. This issue is especially critical in the serrated pathway for colorectal carcinogenesis since it is not as clearly discerned as the conventional adenoma-carcinoma. Furthermore, making the immune surveillance awake against tumor is now considered as a breakthrough in cancer treatment and the serrated pathological pathway comprises two CRC subtypes with typical weak (SAC) and abundant (hMSI-H) immune responses. Therefore, it is crucial to characterize the biology of these tumors since no previous studies have compared their molecular signatures.
2018-06-27 | GSE116305 | GEO
Project description:Serrated adenocarcinomas are morphologically different from conventional adenocarcinomas. The serrated pathway has recently been proposed to represent a novel mechanism of colorectal cancer (CRC) formation. However, whether they are biologically different and truly form a distinct subclass of CRC, is not known. This study shows that the gene expression profile of serrated and conventional CRCs differs from each others and that serrated CRCs are not only morphologically novel, but also biologically distinct subclass of CRC. Keywords: molecular classification
2006-07-28 | GSE4045 | GEO
Project description:Fusobacteria are associated with colorectal cancer (CRC) and are amplified during colorectal carcinogenesis. Compared to the adenoma-carcinoma sequence of carcinogenesis, serrated neoplasm has distinct clinical features and a different molecular background. We aimed to compare the gut microbiome between tubular adenoma (TA) and sessile serrated adenoma/polyp (SSA/P). Patients with TA, SSA/P, or CRC were recruited. Three pieces of colorectal mucosal tissue were obtained from each patient by endoscopic biopsy. 16S rRNA gene pyrosequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were performed. Among 26 enrolled patients, 8, 10, and 8 had TA, SSA/P, and CRC, respectively. The relative abundance of Fusobacteria did not differ significantly between the TA and SSA/P groups (4.3% and 1.9%, P = 0.739) but was higher in the CRC group (33.8%) than in the TA or SSA/P group, respectively (TA vs. CRC, P = 0.002, false discovery rate [FDR] = 0.023; SSA/P vs. CRC, P < 0.001, FDR = 0.001). PICRUSt revealed that most functions in the TA metagenome were similar to those in the SSA/P metagenome. The gut microbiome, including relative abundance of Fusobacteria, did not differ between TA and SSA/P, suggesting that Fusobacteria may contribute to both the serrated pathway and the adenoma-carcinoma sequence.
| S-EPMC4850483 | biostudies-literature
Project description:Objective: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases, and includes tumours that are amongst the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen activated kinase (MAPK) pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype (CIMP), leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein. Design: We utilise organoid culture combined with CRISPR/Cas9 genome engineering, to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair. Results: Targeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not BrafV600E alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting. Conclusion: We generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.
2018-04-30 | GSE112774 | GEO
Project description:The CpG island methylator phenotype is common in both BRAF mutant colorectal cancer and their precursors, the sessile serrated adenoma (SSA). SSAs acquire dysplasia immediate prior to progressing to invasive cancer. Here we examine the methylome of the remnant non-dysplastic portion of dysplastic sessile serrated adenomas to identify changes that occur immediately prior to the development of overt histological dysplasia.
2019-07-11 | E-MTAB-7854 | biostudies-arrayexpress
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: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.
2016-06-01 | GSE79460 | GEO
Project description:BackgroundAltered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma (SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSI-H) are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally different immune response and clinical outcome. However, there are no studies comparing the methylome of these two subtypes of colorectal carcinomas. The methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 48 colorectal specimens, including 39 SACs and 9 matched hmMSI-H.ResultsMicroarray data comparing SAC and hmMSI-H showed an enrichment in functions related to morphogenesis, neurogenesis, cytoskeleton, metabolism, vesicle transport and immune response and also significant differential methylation of 1540 genes, including CD14 and HLA-DOA which were more methylated in hmMSI-H than in SAC and subsequently validated at the CpG, mRNA and protein level using pyrosequencing, quantitative polymerase chain reaction (qPCR) and immunohistochemistry.ConclusionsThese results demonstrate particular epigenetic regulation patterns in SAC which may help to define key molecules responsible for the characteristic weak immune response of SAC and identify potential targets for treating SAC, which lacks molecular targeted therapy.
| S-EPMC6230233 | biostudies-literature
Project description:Previous reports have indicated that RNA m6A modification plays an important role in colorectal carcinogenesis. We hypothesized that F. nucleatum promoted colorectal carcinogenesis dependent on RNA m6A alterations. To test this hypothesis, we conducted a RNA-seq analysis in HT29 cells cocultured with F. nucleatum and medium control.
2022-12-01 | GSE191257 | GEO