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Anti-apoptotic genes and non-coding RNAs are potential outcome predictors for ulcerative colitis

ABSTRACT: Due to the lack of clinical, immunologic, genetic and laboratory markers to predict remission without relapse, there is no clear recommendation regarding withdrawal of therapy. Therefore, this study was to investigate if transcriptional analysis together with Cox survival analysis might be able to reveal molecular markers that are specific for remission duration and outcome. Mucosal biopsies from patients in remission, with active treatment-naïve ulcerative colitis and healthy control subjects underwent whole-transcriptome RNA-seq. Principal component analysis (PCA) and Cox proportional hazards regression analysis was applied to the remission data concerning duration and status of patients. A randomly chosen remission sample set was used for validation of the applied methods and results. The analyses distinguished two different UC remission patient groups with respect to remission duration and outcome (relapse). Both groups showed that altered states of UC with quiescent microscopic disease activity still present. The patient group with the longest remission duration and no relapse revealed specific and increased expression of antiapoptotic factors belonging to the MTRNR2-like gene family and non-coding RNAs. In summary, the expression of anti-apoptotic factors and non-coding RNAs may contribute to personalized medicine approaches in UC by improving patient stratification for different treatment regimens.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169360 | GEO | 2023/05/24

REPOSITORIES: GEO

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Transcriptional signatures that define Ulcerative Colitis in remission

Project description:Background: This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission apart from the existing endoscopic, histologic, and laboratory scoring systems. For that purpose, a well-stratified UC patient population in remission was compared to active UC and control patients and was investigated by applying the next-generation technology RNA-Seq. Methods: Mucosal biopsies from patients in remission (n = 14), patients with active UC (n = 14), and healthy control patients (n = 16) underwent whole-transcriptome RNA-Seq. Principal component analysis, cell deconvolution methods, gene profile enrichment, and pathway enrichment methods were applied to define a specific transcriptional signature of UC in remission. Results: Analyses revealed specific transcriptional signatures for UC in remission with increased expression of genes involved in O-glycosylation (MUC17, MUC3A, MUC5AC, MUC12, SPON1, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHA10, EPHA1), GAP junction trafficking (TUBA1C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLR1, TLR3, TLR5, TLR6). Conclusions: This study reveals specific transcriptional signatures for remission. Partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions were observed. A clear role for bacterial gut flora composition can be implied. The results can be useful for the development of treatment strategies for UC in remission and may be useful targets for further investigations aiming to predict the outcome of UC in the future.

2020-01-18 | GSE128682 | GEO

Transcription profiling by array of diagnosis and relapse specimens of paediatric patients with acute lymphoblastic leukaemia (ALL) to identify mechanisms and pathways of therapy failure

Project description:Gene expression profiles were compared between diagnosis and relapse specimens of paediatric patients with acute lymphoblastic leukaemia (ALL) to identify mechanisms and pathways of therapy failure. The following descriptions provide further information on the annotations applied in this submission: Day 7 MRD- Minimal residual disease (MRD) measured at Day 7 after treatment initiation. Day 14 MRD- MRD measured at day 14 after treatment initiation. End of Induction MRD- MRD at the end of remission induction therapy. Event- Clinical event that is used to interpret patient outcome and used to determine relapse status. Relapse status- The relapse status of the patient which is used to model kaplan-meier survival curves in the related manuscript. Status 0 indicates non-relapse status (patient didn't relapse within time monitored), and 1 indicates relapse. Relapse-Free Survival- The length of time that the patients were relapse-free, or the length of time they were studied for, if they did not relapse. Paired Specimen- Many of the specimens in this study were diagnosis and relapse specimens from the same patient (i.e. Specimens taken at different times). This factor indicates which of the specimens were matched to each other in this way i.e. Which came from the same patient.

2012-07-13 | E-MTAB-1216 | biostudies-arrayexpress

RNA-Seq analysis of gene expression in 25 cases of canine lymphoma undergoing CHOP chemotherapy

Project description:Canine lymphoma is the most common hematological cancer in dogs and shares many molecular and clinical characteristics with human Non-Hodgkin lymphoma (NHL). The standard treatment for canine lymphoma is the “CHOP” sequential multiagent chemotherapy protocol consisting of Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Vincristine (Oncovin™), and Prednisone. Approximately 70 - 85% of patients treated with CHOP achieve clinical remission. However, duration of remission varies and the majority of dogs eventually relapse. To identify possible biomarkers for patients failing to achieve remission in response to CHOP, we performed RNA-Seq analysis on 25 cases of canine lymphoma taken at the start of their CHOP therapy regime, and determined patient progression free survival (PFS).

2020-01-01 | GSE130874 | GEO

Gene expression profiles associated with pediatric relapsed AML

Project description:In high income countries 90% of the patients achieve complete remission after induction chemotherapy. However, 30-40% of these patients suffer from relapse. These patients face a dismal prognosis, as the majority (>60%) of relapsed patients die within 5 years. As a result, outcome for pediatric acute myeloid leukemia (AML) patients remains poor and has stabilized over the past 15 years. To prevent or better treat relapse of AML is the best option to improve outcome. Despite patient specific differences, most patients do respond to initial therapy. This suggests that at relapse, mechanisms are active that cause the altered response to chemotherapy. Detailed understanding of mechanisms that cause relapse remain largely elusive. To gain insight in the molecular pathways that characterize relapsed AML, we performed genome wide gene expression profiling on paired initial diagnosis and relapsed AML samples of 23 pediatric AML patients. We used pathway analysis to find which molecular pathways are involved in altered gene expression between diagnosis and relapse samples of individual AML patients. 23 paired diagnosis and relapse bone marrow or peripheral blood samples were collected and cryo-preserved. They were later thawed and processed for hybridization to Affymetrix U133 Plus 2.0 arrays.

2015-05-07 | E-GEOD-52891 | biostudies-arrayexpress

Gene expression profiles associated with pediatric relapsed AML

2015-05-07 | GSE52891 | GEO

Longitudinal Study of Transcriptomic Changes Occurring Over the Course of CHOP Treatment in Canine Lymphoma

Project description:The standard treatment for canine lymphoma (cL) is the CHOP chemotherapy protocol. Most cL patients treated with CHOP initially achieve remission but the duration varies and the majority of dogs eventually relapse with a multidrug resistant phenotype. This study assesses changes in gene expression occurring in cL tumor cell populations over the course of CHOP treatment. We measured gene expression using RNA-Seq on 15 cL patient samples taken prior to treatment and again 6 weeks into treatment.

2021-07-14 | GSE179920 | GEO

The Evolving Immune Microenvironment of B-cell Acute Lymphoblastic Leukemia [human bone marrow dataset]

Project description:Single-cell RNA-seq analysis of primary human bone marrow immune populations isolated from B-ALL patient samples (matched diagnosis, remission and relapse), and healthy bone marrow donor samples.

2020-06-08 | GSE130116 | GEO

The Evolving Immune Microenvironment of Human B-cell Acute Lymphoblastic Leukemia [CITE-Seq]

2020-06-26 | GSE153358 | GEO

Small nucleolar RNA and microRNA expression data from multiple sclerosis patients in relapse and remission.

Project description:Multiple sclerosis is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes in leucocytes, and miRNA altered in remission are involved in the regulation of innate immunity. We observed that sncRNA dysregulation is different in relapse and remission leading to differences in transcriptome regulation, and that this process is sex dependent. In conclusion, relapse and remission have a different molecular background in men and women. 24 multiple sclerosis patients with samples both in remission and relapse (2 samples for each patient; 48 blood samples in total) and 24 healthy controls were included in the study, for a total of 72 samples.

2015-11-03 | E-GEOD-74579 | biostudies-arrayexpress

Discovery of biomarker candidates associated with the risk of short- and long-term relapse after infliximab withdrawal in Crohns patients: a proteomics-based study

Project description:Objective: A subset of Crohns disease (CD) patients experiences long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.Design: New biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (STORI cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short- (<6 months) or long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs. Results: Distinct biomarker candidates were associated with the risk (hazard ratio: HR) of short- (15 proteins, 2.9<HR<16.1, p<0.05) and long-term (17 proteins, 2<HR<4.4, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (FDR<0.001) than CRP and faecal calprotectin (current references in predicting relapse). Conclusion: We identified for the first time circulating biomarker candidates associated with the risk of long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating anti-TNFα withdrawal in CD patients.

2020-10-19 | PXD019008 | Pride

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