IBDCA Edinburgh
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ABSTRACT:
PROVIDER: EGAS00001001129 | EGA |
REPOSITORIES: EGA
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Project description:In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.
| EGAD00001001330 | EGA
Project description:Background: Hodgkin lymphoma (HL) and testicular cancer (TC) survivors have an increased risk of developing second primary bowel malignancies (both colorectal cancer (CRC) and small bowel adenocarcinoma (SBA)). We aimed to determine differences in genetic characteristics of second primary bowel malignancies and primary bowel malignancies.
Methods: Copy number aberrations (CNAs) generated by low-coverage whole-genome sequencing (WGS) were collected from previous studies of second primary CRC (HL survivors, n=39), primary CRC (n=90) and primary SBA (n=14). In addition, seven new samples of second primary SBA from HL (n=3) or TC (n=5) survivors, identified in the Dutch national pathology registry (PALGA), were available for low-coverage WGS.
Results: Overall, CNA patterns observed in second primary bowel malignancies were similar to those in primary bowel malignancies. Losses of 21q22.2 were observed more frequently (p=0.057) in second primary CRC compared with primary CRC, while in second primary SBA gains of 10p15.3-15.1 and losses of 18q12.1-23 were significantly more frequent detected compared with primary SBA.
Conclusions: Second primary CRC and SBA show comparable genome wide CNAs to those in primary CRC and SBA, respectively. This suggests that part of the pathogenesis of second primary tumours in these cancer survivors is similar to those of primary CRC and SBA in general, despite the exposure to DNA damaging treatments received for earlier HL and TC.
| EGAS00001005940 | EGA
Project description:Early detection of colorectal cancer (CRC) and distinguishing inflammatory bowel diseases from cancerous conditions significantly improve survival rates. While colonoscopy is the gold standard for CRC detection, it is invasive and associated with potential complications. Therefore, there is a need for blood biomarkers that possess high sensitivity and specificity which can be used for pre-diagnosis. In this study, we screened for serum biomarkers specifically altered in colonoscopy-positive (CP) patients (cancer group) when compared to colonoscopy-negative (CN) patients (suffering from other bowel-related illnesses with symptoms similar to CRC), and healthy control (HC) individuals (n=20 each). Using Data-Independent Acquisition-Mass spectrometry (DIA-MS) analysis, we identified potential protein markers and neoantigens uniquely altered in the CP group compared to the CN group.
2025-06-10 | PXD055218 | Pride
Project description:Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans. Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans. The study investigated transcription levels in human colon biopsies obtained during a colonoscopic exam in 32 subjects suffering from either inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). IBS patients served as control patients for comparison with IBD patients (see Study 1). 12 of these patients (6 IBD and 6 IBS) also followed a 7-day diet high in red meat (300 grams/day) after which a second colonscopic exam was performed to obtain colon biopsies to investigate the effect of the red meat intervention (Study 2). For each subject, cRNA copies of mRNA isolated from the colon biopsies were labeled with one dye (Cy3) and each sample was hybridized on a separate array. One replicate per subject or before/after red meat intervention (so 44 arrays in total, i.e. 20 before patients and 12 before and after patients).
2011-02-01 | E-GEOD-25220 | biostudies-arrayexpress
Project description:MicroRNA deregulation is frequent in human colorectal cancers (CRCs) but little is known to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b over-expression is triggered in mouse and humans by APC loss, PTEN/PI3K pathway deregulation and by SRC over-expression and promotes tumor transformation and progression. We show that miR-135b up-regulation is common to sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth controlling genes involved in proliferation, invasion and apoptosis. We identify miR-135b as a key down-steam effector of oncogenic pathways and a potential novel target for CRC patientM-bM-^@M-^Ys treatment. RNA was extracted using trizol from normal human colon cell lines comparing scrambled with miR-135b oligos transfected cells
2014-01-17 | E-GEOD-54163 | biostudies-arrayexpress
Project description:MicroRNA deregulation is frequent in human colorectal cancers (CRCs) but little is known to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b over-expression is triggered in mouse and humans by APC loss, PTEN/PI3K pathway deregulation and by SRC over-expression and promotes tumor transformation and progression. We show that miR-135b up-regulation is common to sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth controlling genes involved in proliferation, invasion and apoptosis. We identify miR-135b as a key down-steam effector of oncogenic pathways and a potential novel target for CRC patient’s treatment. RNA was extracted from fresh frozen tissues from tumours from APC;CpC and AOM/DSS mice and normal matched tissues
2014-01-17 | E-GEOD-54177 | biostudies-arrayexpress
Project description:Early detection of colorectal cancer (CRC) and distinguishing inflammatory bowel diseases from cancerous conditions significantly improve survival rates. While colonoscopy is the gold standard for CRC detection, it is invasive and associated with potential complications. Therefore, there is a need for blood biomarkers that possess high sensitivity and specificity which can be used for pre-diagnosis. In this study, we screened for serum biomarkers specifically altered in colonoscopy-positive (CP) patients (cancer group) when compared to colonoscopy-negative (CN) patients (suffering from other bowel-related illnesses with symptoms similar to CRC), and healthy control (HC) individuals (n=20 each). Using Data-Independent Acquisition-Mass spectrometry (DIA-MS) analysis, we identified potential protein markers and neoantigens uniquely altered in the CP group compared to the CN group. These biomarkers were validated using a targeted approach, Parallel Reaction Monitoring-Mass Spectrometry (PRM-MS). An independent set of samples (n=10 each) was taken for all the groups.
2025-06-23 | PXD065161 | Pride
Project description:Colorectal cancer (CRC) is among the best examples depicting the relationship between inflammation and increased cancer risk. The introduction of new therapeutic options targeting the inflammatory mediators has been shown to markedly decrease the overall risk of CRC even though their chemopreventive potential is still under debate [1,2]. Specifically, conflicting reports exist concerning the relationship between Infliximab, a monoclonal antibody that specifically blocks Tumor Necrosis Factor (TNF), and an increased risk of CRC in patients with Inflammatory Bowel Disease (IBD). To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie-ApcMin/+ line. Surprisingly, a detailed histological characterization, demonstrated that the deletion of Tnf in Winnie-ApcMin/+ mice resulted in an initial reduction of dysplastic lesions incidence in 5-week-old mice, followed by faster disease progression with a unique molecular pattern at 8 weeks. Our results highlight that TNF could exert a dual role in CAC supporting the promotion of neoplastic lesions onset at the early stage of the disease and inducing their reduction during disease progression.
2023-05-01 | E-MTAB-12356 | biostudies-arrayexpress
Project description:Purpose: Celiac disease (CD) is a risk factor for developing Small Bowel Carcinoma (SBC) with a 14 folds higher risk than that of the general population. As SBCs associated with CD (CD-SBCs) are extremely rare, very few molecular data are currently available about their pathogenesis and information about CD-SBC transcriptomic profiling is completely lacking. Patients and Methods: We generated RNA-seq data on 13 CD-SBCs selected from the largest and well-characterized series of CD-SBCs published so far that was collected by the Small Bowel Cancer Italian Consortium. In all cases we compared the CD-SBC transcriptional signatures with the four consensus molecular subtypes (CMS) of colorectal carcinoma (CRC) applying the ‘CMS classifier’. CpG Island Methylator Phenotype (CIMP+) was evaluated in all cases using methylation-sensitive multiple ligation-dependent probe amplification. Results: RNA-based signatures of CD-SBCs exhibited strong similarities with CRCs. Twelve of 13 CD-SBCs (92%) fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e. CMS1 and CMS4. CMS1 CD-SBCs (62% of cases) were commonly MSI/CIMP+ tumors and showed increased expression of genes associated with a diffuse TH1 and cytotoxic T immune infiltrate, up-regulation of apoptosis, cell cycle progression and proteasome pathways. CMS4 CD-SBCs (31% of cases) showed prominent TGF-β activation and were characterized by complement-associated inflammation, matrix remodeling, stromal invasion and angiogenesis Conclusions: RNA-based signatures of CD-SBCs strongly recapitulate CMS classification of CRC, give a promising tool to improve our knowledge of this rare entity and provide clinically useful information using the wealth of data available for CRC.
2020-03-01 | E-MTAB-7760 | 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, 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. This profiling is based on the analysis of 4 donors who underwent curative large bowel resection for CRC from 1 to 19 years before (M-CRC samples), 4 disease-free carriers of mutations in the mismatch repair system genes, who are predisposed to develop HNPCC (HNPCC samples) and 4 endoscopy-negative, asymptomatic individuals (NOR samples)
2013-11-30 | E-GEOD-23011 | biostudies-arrayexpress