Transcriptional analysis of left-sided colitis, pancolitis and ulcerative colitis-associated dysplasia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE47908 | GEO | 2014/12/31
SECONDARY ACCESSION(S): PRJNA208298
REPOSITORIES: GEO
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Project description:Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed “loss of gradient” reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 – 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
2020-09-16 | PXD018679 | Pride
Project description:Samples were taken from either surgically resected specimens or during surveillance colonoscopic examination. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting development of cancer and/or dysplasia in ulcerative colitis, and to characterize potential diagnostic markers in UC-associated neoplasm. Experiment Overall Design: 43 UC-NonCa, 10 UC-Ca, 60 sporadic-Ca and 6 UC-associated Ca were analyzed
2008-06-12 | E-GEOD-3629 | biostudies-arrayexpress
Project description:Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Colitis-associated dysplasia (flat or polypoid) continues to be a reliable marker for CRC in these patients. However, flat lesions are often missed during endoscopy and can rapidly progress to high-grade dysplasia or cancer. microRNAs (miRs), small non-coding RNAs, have emerged as a valuable diagnostic biomarker of human cancer due to their ease of detection and stability. The goal of this study was to identify a miR signature that can serve as a reliable biomarker for the early detection of colitis-associated dysplasia in patients with long-standing colitis.
2022-07-23 | GSE209581 | GEO
Project description:Background and Aims: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer, although underlying mechanisms are incompletely understood. We sought to identify a potential gene expression signature in non-dysplastic distal mucosa that as a “genetic field effect” could be a marker for remote neoplastic lesions. Results: 468 genes were significantly up-regulated and 541 genes were significantly down-regulated >2-fold in UC patients with neoplasia compared to UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly up-regulated from controls to quiescent non-dysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increases in tissue expression of S100A9 and REG1 in UC-associated cancer and in non-dysplastic tissue from UC patients harboring remote neoplasia, compared to UC patients without dysplasia and normal controls. Conclusions: Gene expression changes occur as a field effect in UC patients without active inflammation who harbor a remote dysplastic lesion. Further characterization of these genes and proteins might elucidate pathways of carcinogenesis in IBD and lead to the development of more accurate, less invasive markers of dysplasia in those at increased risk. Microarray assay were conducted on 20 RNA samples isolated from colon mucosa of 20 patients. Of these patients, 5 were normal controls, 4 had quiescent UC, and 11 had UC with neoplasia. Patients were included if they had a previous clinical diagnosis of UC confirmed by an expert GI pathologist, a disease duration > 7 years, and an extent of disease >20 cm proximal to the anal verge.
2012-04-19 | E-GEOD-37283 | biostudies-arrayexpress
Project description:Background and Aims: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer, although underlying mechanisms are incompletely understood. We sought to identify a potential gene expression signature in non-dysplastic distal mucosa that as a “genetic field effect” could be a marker for remote neoplastic lesions. Results: 468 genes were significantly up-regulated and 541 genes were significantly down-regulated >2-fold in UC patients with neoplasia compared to UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly up-regulated from controls to quiescent non-dysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increases in tissue expression of S100A9 and REG1 in UC-associated cancer and in non-dysplastic tissue from UC patients harboring remote neoplasia, compared to UC patients without dysplasia and normal controls. Conclusions: Gene expression changes occur as a field effect in UC patients without active inflammation who harbor a remote dysplastic lesion. Further characterization of these genes and proteins might elucidate pathways of carcinogenesis in IBD and lead to the development of more accurate, less invasive markers of dysplasia in those at increased risk.
2012-04-20 | GSE37283 | GEO
Project description:Samples were taken from either surgically resected specimens or during surveillance colonoscopic examination. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting development of cancer and/or dysplasia in ulcerative colitis, and to characterize potential diagnostic markers in UC-associated neoplasm. Keywords: repeat
2007-02-28 | GSE3629 | GEO
Project description:Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains “inflammation-dysplasia-cancer” sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC.
2012-08-02 | GSE31106 | GEO
Project description:Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells, from three left-sided and three right-sided CRC patients were profiled by scRNA-seq. Right-sided CRC harbors a significant proportion of exhausted CD8 T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of “pre-exhausted” to exhausted T cells were favorable prognostic markers. Notably, we identified a novel RBP4+ NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.
2021-11-15 | GSE188711 | GEO
Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.
2008-06-20 | E-GEOD-9452 | biostudies-arrayexpress
Project description:The natural history of Crohn's disease (CD) and ulcerative colitis (UC) is variable. In patients with frequently-relapsing/steroid-refractory disease, sustained remission is more likely if immunomodulators are introduced earlier. However, many patients experience quiescent disease without immunomodulators, and should not be unnecessarily immunosuppressed. Previous attempts to stratify treatment from diagnosis have failed because disease course cannot be reliably predicted. We performed whole genome expression analysis of peripheral CD8 and CD4 T-cells isolated from patients with active, untreated CD or UC. Patients were prospectively managed by clinicians blinded to the microarray results. Analysis of CD8 T-cell gene-expression data revealed two distinct subgroups within each disease cohort, which did not correlate with any contemporaneous laboratory or clinical data. There was considerable overlap in the genes that were differentially expressed between the subgroups in each disease. Patients belonging to one of the subgroups (termed IBD1) experienced significantly more aggressive disease than those in the other (termed IBD2) in both diseases. This was characterised by a greater need to escalate treatment with immunomodulators or surgery in response to relapsing or chronically active disease. Furthermore, this subgroup more frequently required additional interventions due to the initial escalation failing to maintain disease remission. Similar association with disease behaviour could not be demonstrated with CD4 T-cell gene-expression analysis, nor with previously described methods of predicting outcome. Our findings demonstrate that gene-expression profiling of CD8 T-cells at diagnosis can stratify patients with CD or UC according to subsequent disease behaviour and represents a significant step towards personalised therapy.
2011-07-19 | E-MTAB-331 | biostudies-arrayexpress