Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen.
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ABSTRACT:
SUBMITTER: Soomro S
PROVIDER: S-EPMC8239008 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.
| S-EPMC8253849 | biostudies-literature
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:Ulcerative colitis (UC) is a chronic, highly heterogeneous intestinal inflammation with changes in epithelial function and tissue damage. However, the pathogenesis is still unclear between active UC and inactive UC. Herein, weighted gene co-expression network analysis was applied to explore the gene modules related to active UC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to further investigate the underlying mechanism of selected genes. We found that in the blue module (r = -.72), carboxypeptidase A6 (CPA6) was chosen to validate because of its high intra-modular connectivity and module membership. In the test sets, the expression level of CPA6 was down-regulated in active UC compared with inactive UC and normal colon. Furthermore, CPA6 expression was decreased primarily in the descending colon and only in mucosa affected by active UC. The receiver operating characteristic curve indicated that CPA6 expression had a performed well in diagnosing active UC from inactive UC (area under the curve = 0.99). Importantly, anti-tumour necrosis factor (TNF) treatment (infliximab and golimumab) significantly increased the CPA6 expression. Finally, GSEA and GSVA found that extracellular matrix receptor, inflammatory response and epithelial-mesenchymal transition were highly enriched in active UC with low CPA6 expression. In conclusion, CPA6 was identified and validated as a novel potential biomarker for predicting the occurrence of active UC, probably through regulating extracellular matrix or immune response.
| S-EPMC7412415 | biostudies-literature
Project description:BackgroundViral infections have been suggested as possible triggers for the onset of ulcerative colitis (UC).MethodsWe employed VirCapSeq-Vert, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe UC. We surveyed fecal samples collected at presentation, after symptom remission, and from a control group diagnosed with irritable bowel syndrome.ResultsSeventy subjects with UC (mean age 13 years, 45 had moderate symptoms, 25 had severe, 69 of 70 had a Mayo endoscopy subscore 2/3) were studied. We detected a wide range of animal viruses that were taxonomically classified into 12 viral families. A virus was present in 50% of fecal samples collected at presentation, 41% of samples collected after remission, and 40% of samples in our control group. The most frequently identified viruses were diet-based gyroviruses. The UC cohort had a significantly higher prevalence of anelloviruses compared with the control cohort. However, we did not identify a single virus that can be implicated in the onset of UC and did not find an association between UC disease severity and viral presence.ConclusionPresence of virus in stool was not associated with the onset of pediatric UC.
| S-EPMC7108593 | biostudies-literature
Project description:Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non-dysplastic mucosa; we hypothesized that the same field defect will include abnormally expressed proteins. Here we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared from 1) UC patients without dysplasia (non-progressors); 2) none-dysplastic colonic tissue from UC patient with high-grade dysplasia or cancer (progressors); 3) high-grade dysplastic tissue from UC progressors and 4) normal colon. We identified protein differential expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, calcium-binding proteins were some of interesting classes of these proteins. Network analysis discovered that Sp1 and c-myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over-expressed proteins in the non-dysplastic tissue of UC progressors, CPS1 and S100P, were further confirmed by IHC analysis. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non-dysplastic mucosa that identify a patient's risk for UC dysplasia.
| S-EPMC2809935 | biostudies-literature
Project description:BACKGROUND:Vedolizumab is an effective therapy for ulcerative colitis (UC), but costly and slow to work. New clinical responses occur after 30 weeks of therapy. AIMS:To enable physicians, patients, and insurers to predict whether a patient with UC will respond to vedolizumab at an early time point after starting therapy. METHODS:The clinical study data request website provided the phase 3 clinical trial data for vedolizumab. Random forest models were trained on 70% and tested on 30% of the data to predict corticosteroid-free endoscopic remission at week 52. Models were constructed using baseline data, or data through week 6 of vedolizumab therapy from 491 subjects. RESULTS:The AuROC for prediction of corticosteroid-free endoscopic remission at week 52 using baseline data was only 0.62 (95% CI: 0.53-0.72), but was 0.73 (95% CI: 0.65-0.82) when using data through week 6. A total of 47% of subjects were predicted to be remitters, and 59% of these subjects achieved corticosteroid-free endoscopic remission, in contrast to 21% of the predicted non-remitters. A week 6 prediction using FCP ?234 ?g/g was nearly as accurate. CONCLUSIONS:A machine learning algorithm using laboratory data through week 6 of vedolizumab therapy was able to accurately identify which UC patients would achieve corticosteroid-free endoscopic remission on vedolizumab at week 52. Application of this algorithm could have significant implications for clinical decisions on whom to continue on this costly medication when the benefits of the vedolizumab are not clinically apparent in the first 6 weeks of therapy.
| S-EPMC5814341 | biostudies-literature
Project description:ObjectivesTo investigate the characteristics and prognostic value of fecal lactoferrin trajectories in ulcerative colitis (UC).MethodsThis study used data from the UNIFI trial (ClinicalTrials.gov, NCT02407236) and included patients who received ustekinumab during induction for trajectory modeling (n = 637). Patients who received ustekinumab during maintenance therapy were used for 1-year outcome analyses (n = 403). The levels of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were measured at weeks 0, 2, 4, and 8. The trajectories of these biomarkers were developed using a latent class growth mixed model.ResultsThe trajectories of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were distinct, but all were associated with prior exposure to anti-tumor necrosis factor agents and vedolizumab. Furthermore, the fecal lactoferrin trajectory was the most valuable predictor of endoscopic, clinical, and histological remission. Compared to the high/moderate-rapid decrease trajectory group, the moderate-slow decrease, high-slow decrease, and high-stable groups had adjusted odds ratios (95% confidence interval) of 0.38 (0.18, 0.78; P = 0.010), 0.47 (0.23, 0.93; P = 0.032), and 0.33 (0.17, 0.63; P = 0.001), respectively, of 1-year endoscopic remission. Patients with high/moderate-rapid decrease trajectories also had the highest likelihood of achieving clinical and histological remission. Finally, we developed a patient-stratification scheme based on fecal lactoferrin trajectories and concentrations. Patients with good, moderate, and poor prognoses in the scheme had a distinct probability of achieving 1-year endoscopic remission (52.7%, 30.9%, and 12.8%, respectively).ConclusionsThe trajectory of fecal lactoferrin is a valuable prognostic factor for 1-year remission in UC.
| S-EPMC10680133 | biostudies-literature
Project description:Background & aimsPatients with chronic ulcerative colitis are at increased risk for colorectal neoplasia (CRN). Surveillance by white-light endoscopy (WLE) or chromoendoscopy may reduce risk of CRN, but these strategies are underused. Analysis of DNA from stool samples (sDNA) can detect CRN with high levels of sensitivity, but it is not clear if this approach is cost-effective. We simulated these strategies for CRN detection to determine which approach is most cost-effective.MethodsWe adapted a previously published Markov model to simulate the clinical course of chronic ulcerative colitis, the incidence of cancer or dysplasia, and costs and benefits of care with 4 surveillance strategies: (1) analysis of sDNA and diagnostic chromoendoscopy for patients with positive results, (2) analysis of sDNA with diagnostic WLE for patients with positive results, (3) chromoendoscopy with targeted collection of biopsies, or (4) WLE with random collection of biopsies. Costs were based on 2014 Medicare reimbursement. The primary outcome was the incremental cost-effectiveness ratio (incremental cost/incremental difference in quality-adjusted life-years) compared with no surveillance and a willingness-to-pay threshold of $50,000.ResultsAll strategies fell below the willingness-to-pay threshold at 2-year intervals. Incremental cost-effectiveness ratios were $16,362 per quality-adjusted life-year for sDNA analysis with diagnostic chromoendoscopy; $18,643 per quality-adjusted life-year for sDNA analysis with diagnostic WLE; $23,830 per quality-adjusted life-year for chromoendoscopy alone; and $27,907 per quality-adjusted life-year for WLE alone. In sensitivity analyses, sDNA analysis with diagnostic chromoendoscopy was more cost-effective than chromoendoscopy alone, up to a cost of $1135 per sDNA test. sDNA analysis remained cost-effective at all rates of compliance; when combined with diagnostic chromoendoscopy, this approach was preferred over chromoendoscopy alone, when the specificity of the sDNA test for CRN was >65%.ConclusionsBased on a Markov model, surveillance for CRN is cost-effective for patients with chronic ulcerative colitis. Analysis of sDNA with chromoendoscopies for patients with positive results was more cost-effective than chromoendoscopy or WLE alone.
| S-EPMC5108686 | biostudies-literature
Project description:Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
| S-EPMC6487890 | biostudies-literature