MiRNA expression in human colitis-associated dysplasia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209581 | GEO | 2022/07/23
REPOSITORIES: GEO
Similar Datasets
Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions. FFPE colorectal tissue samples of 35 polypoid adenomas and 83 flat adenomas. Test samples were compared to an external pool of normal male/female reference DNA.
2012-10-04 | E-GEOD-30479 | biostudies-arrayexpress
Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions.
2012-10-04 | GSE30479 | GEO
Project description:Colorectal cancer (CRC) is a genetically heterogeneous disease with several distinct morphological growth patterns. This study was aimed to investigate genes differentially expressed between ulcerative and polypoid colorectal CRC. cDNA microarray was first employed to compare the gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa. Potential candidates identified by data filtering were further validated using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray identified 11 up-regulated and 14 down-regulated genes differentially expressed in both types of tumor compared to matched normal mucosa. Among them, S100P was the only upregulated gene preferentially associated with polypoid CRC (p = 0.032), whereas no genes demonstrated significantly differential association with ulcerative CRC. S100P protein and mRNA expression level of polypoid CRC was significantly higher than that of ulcerative CRC (p < 0.05, respectively). Immunoreactivity of S100P protein was localized predominantly in the nuclei and to a less extent in the cytoplasm. Overexpression of S100P occurred early in the adenoma stage. 80% (24/30) and 20% (6/30) polypoid CRC showed diffusely strong and moderate overexpression, respectively. In contrast, S100P was diffusely and strongly expressed in 15% (6/40) ulcerative CRC, with 52.5% (21/40) and 32.5% (13/40) tumors having moderate and weak overexpression, respectively. S100P overexpression was preferentially associated with polypoid CRC (p < 0.001). The relative methylation level determined by MSP was not statistically different between polypoid and ulcerative CRC (43.36% vs. 49.10%, p = 0.168), indicating that promoter hypomethylation was directly related to upregulation of S100P mRNA. The gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa were compared. Dye swapping experiments with ulcerative CRC vs normal mucosa or polypoid CRC vs normal mucosa were performed and we averaged the log ratios of the duplicated spots on each slide.
2013-05-16 | E-GEOD-46905 | biostudies-arrayexpress
Project description:Interventions: 1. Clinical data registration;
2. Molecular analysis of polypoid vs. flat colorectal lesions.
Primary outcome(s): 1. Prevalence of flat colorectal lesions in a Dutch population;
2. Clinical characteristics (e.g. location of lesions, percentage of high-grade dysplasia or early cancer);
3. Molecular charcteristics (epigenetic: methylation status and genetic) of flat vs. polypoid colorectal lesions;
4. Prevalence of flat advanced colorectal cancers vs. polypoid advanced colorecal cancers: clinical features of these lesions (e.g. tumor stage);
5. Relation between serrated and adenomatous polyps.
Study Design: Non-randomized controlled trial, Open (masking not used), N/A , unknown, Factorial
| 16199 | ecrin-mdr-crc
Project description:Colorectal cancer (CRC) is a genetically heterogeneous disease with several distinct morphological growth patterns. This study was aimed to investigate genes differentially expressed between ulcerative and polypoid colorectal CRC. cDNA microarray was first employed to compare the gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa. Potential candidates identified by data filtering were further validated using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray identified 11 up-regulated and 14 down-regulated genes differentially expressed in both types of tumor compared to matched normal mucosa. Among them, S100P was the only upregulated gene preferentially associated with polypoid CRC (p = 0.032), whereas no genes demonstrated significantly differential association with ulcerative CRC. S100P protein and mRNA expression level of polypoid CRC was significantly higher than that of ulcerative CRC (p < 0.05, respectively). Immunoreactivity of S100P protein was localized predominantly in the nuclei and to a less extent in the cytoplasm. Overexpression of S100P occurred early in the adenoma stage. 80% (24/30) and 20% (6/30) polypoid CRC showed diffusely strong and moderate overexpression, respectively. In contrast, S100P was diffusely and strongly expressed in 15% (6/40) ulcerative CRC, with 52.5% (21/40) and 32.5% (13/40) tumors having moderate and weak overexpression, respectively. S100P overexpression was preferentially associated with polypoid CRC (p < 0.001). The relative methylation level determined by MSP was not statistically different between polypoid and ulcerative CRC (43.36% vs. 49.10%, p = 0.168), indicating that promoter hypomethylation was directly related to upregulation of S100P mRNA.
2013-05-16 | GSE46905 | GEO
Project description:To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors. 4 samples of individual distal colitis-associated tumors (CAC) from 4 mice, 2 samples of tumor-free distal colon epithelium with a pool of 5 mice per sample (CAC contr), 5 samples of individual Apcmin/+ tumors from the distal colorectum of 5 mice (sporCRC) and 3 samples of tumor-free distal colon epithelium (pool of 4 mice per sample) (sporCRC contr). Colitis-associated tumorigenesis was performed by intraperitoneal injection of Azoxymethane (10mg/kg) (Sigma) into C57BL/6J wildtype mice followed by 3 cycles of Dextran Sodium Sulfate (DSS) in drinking water. Each DSS-cycle was composed of DSS (2.5% (w/v) (MP Biomedicals) in drinking water for 7 days, followed by a recovery phase with regular drinking water for 14 days. Sporadic tumors were from C57BL/6J-ApcMin/+/J mice. All tumors were obtained from the from the lower 6th of the large intestine and they had the same size covering between ¼ and up to ½ of the colonic circumferenc as evaluated by mini-endoscopy.
2013-04-01 | E-GEOD-43338 | biostudies-arrayexpress
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets
2021-09-09 | PXD021318 | Pride
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets.
2021-09-09 | PXD021314 | Pride
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 (NOR), 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 (MCRC) (GSE23011). As test set we run on affymetrix arrays an independent set of mucosal biopsies of MCRC and NOR samples. This profiling is based on the analysis of 5 patients who underwent curative large bowel resection for CRC from 1 to 15 years before (MCRC samples), and 12 endoscopy-negative, asymptomatic individuals (NOR samples)
2013-11-30 | E-GEOD-23194 | 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