Molecular analysis of cancers in the large intestine in patients that use statins.
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Carcinoma, Statins/statines, Bmp, Smad4, Chemoprevention
PROVIDER: 15779 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: None: niet WMO-plichtig onderzoek.
Retrospective analysis of clinical and pathology records, and molecular analysis on resection specimen.
Primary outcome(s): 1. Prevalence of interval CRCs in a Dutch population;
2. Clinical characteristics;
3. Molecular characteristics;
4. Differences with non-interval CRCs.
Study Design: N/A: single arm study, N/A , unknown, Parallel
| 17347 | ecrin-mdr-crc
Project description:Background: COPD is currently the fourth leading cause of death worldwide and predicted to rank third by 2020. Statins are commonly used lipid lowering agents with documented benefits on cardiovascular morbidity and mortality, and have also been shown to have pleiotropic effects including anti-inflammatory and anti-oxidant activity. Objective: Identify a gene signature associated with statin use in the blood of COPD patients, and identify molecular mechanisms and pathways underpinning this signature that could explain any potential benefits in COPD. Methods: Whole blood gene expression was measured on 168 statin users and 452 non-users from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study. Gene expression was measured using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS) was used to process the expression data and to filter out non-informative probe sets. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma) package adjusting for propensity score and employing a surrogate variable analysis. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser. Results: 18 genes were differentially expressed between statin users and non-users at a false discovery rate of 10%. Top genes included LDLR, ABCA1, ABCG1, MYLIP, SC4MOL, and DHCR24. The 18 genes were significantly enriched in pathways and biological processes related to cholesterol homeostasis and metabolism, and were enriched for transcription factor binding sites for sterol regulatory element binding protein 2 (SREBP-2). The resulting gene signature showed correlation with Huntington disease, Parkinson’s disease and acute myeloid leukemia. Conclusion: Statins gene signature was not enriched in any pathways related to respiratory diseases, beyond the drug’s effect on cholesterol homeostasis. Study subjects were a subset of those with COPD from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study (Vestbo et al.), funded by GlaxoSmithKline (GSK Study No. SCO104960, NCT00292552). ECLIPSE is a non-interventional, observational, multicentre, three-year study in people with COPD. Blood was collected in PAXGene tubes and frozen at -80oC. In this work we have looked at the effect of statins on gene expression in 620 subjects of whom 168 were statin users. ECLIPSE study was described in: Vestbo J, Anderson W, Coxson HO, et al.: Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). Eur Respir J. 2008;31(4):869-73
2015-07-23 | E-GEOD-71220 | biostudies-arrayexpress
Project description:Background: COPD is currently the fourth leading cause of death worldwide and predicted to rank third by 2020. Statins are commonly used lipid lowering agents with documented benefits on cardiovascular morbidity and mortality, and have also been shown to have pleiotropic effects including anti-inflammatory and anti-oxidant activity. Objective: Identify a gene signature associated with statin use in the blood of COPD patients, and identify molecular mechanisms and pathways underpinning this signature that could explain any potential benefits in COPD. Methods: Whole blood gene expression was measured on 168 statin users and 452 non-users from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study. Gene expression was measured using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS) was used to process the expression data and to filter out non-informative probe sets. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma) package adjusting for propensity score and employing a surrogate variable analysis. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser. Results: 18 genes were differentially expressed between statin users and non-users at a false discovery rate of 10%. Top genes included LDLR, ABCA1, ABCG1, MYLIP, SC4MOL, and DHCR24. The 18 genes were significantly enriched in pathways and biological processes related to cholesterol homeostasis and metabolism, and were enriched for transcription factor binding sites for sterol regulatory element binding protein 2 (SREBP-2). The resulting gene signature showed correlation with Huntington disease, Parkinson’s disease and acute myeloid leukemia. Conclusion: Statins gene signature was not enriched in any pathways related to respiratory diseases, beyond the drug’s effect on cholesterol homeostasis.
2015-07-23 | GSE71220 | GEO
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:Background: The microbiome is increasingly being linked to cancer risk. Little is known about the lung and oral cavity microbiomes in healthy smokers (SM), and even less for electronic cigarette (EC) users, compared healthy never-smokers (NS). Methods: In a cross-sectional pilot study of SM (N=8), EC users (N=10) and NS (N=10) saliva and bronchoscopy-collected bronchoalveolar lavage samples were collected. Bacteria species were identified through metatranscriptome profiling by RNA-sequencing to study associations with the lung and oral microbiome. Pairwise comparisons and linear modeling was assessed with false discovery rates <0.1. Results: Total bacterial load was similar for the SM, EC users and NS, and there was no differences in the bacterial diversity across groups. In the lung, there were 44 bacterial species that were statistically significantly different for SM/NS, 80% of which were decreased in the SM. There were 12 bacterial species that were different for SM/EC users, all of which were decreased, 10 of which were also identified in the SM/NS comparison. The 2 bacterial species unique to SM/EC comparison were Neisseria sp. KEM232 and Curvibacter sp. AEP1-3. From the top 5 decreased species in SM/EC, 3 were also identified in the SM/NS comparison (Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae) and 2 of these were unique to the SM/EC comparison (Neisseria zoodegmatis and Ottowia sp. oral taxon 894). There were 8 species increased in SM compared to NS, none of which are known to be clinically significant. In the oral microbiome, 152 bacteria species were differentially abundant for the SM/NS analysis, and only 17 for the EC/NS comparison, all which were also present in SM/NS comparisons. There were 21 bacteria that were differentially abundant in both the lung and oral cavity for SM and NS, 95% also were decreased in the SM. Conclusion: Smoking and EC use do not appear to materially affect the lung microbiome, although differences are noted of unclear clinical significance. Most differentially abundant bacteria decreased, which may be due to a toxic effect of cigarette smoke, including a change in humidity or heating. Given the low number of overlapping oral and lung microbes, the oral microbiome does not appear to be a good surrogate for smoking-related effects in the lung.
2022-07-13 | GSE180785 | GEO
Project description:Transcriptomic analysis reveals a statin-induced core molecular signature in human iPSC-CMs
| PRJNA451485 | ENA
Project description:Interventions: Four Groups:None
Primary outcome(s): Intestinal microflora
Study Design: Case-Control study
| 2676442 | ecrin-mdr-crc
Project description:Genome wide DNA methylation profiling of fresh frozen, histologically normal-appearing breast tissue from the Normal Breast Study (NBS). The Illumina HumanMethylation450 BeadChip was used to obtain DNA methylation profiles for 90 samples, including “current”, “former” and never users of HRT.
2017-12-19 | GSE108213 | GEO
Project description:The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.
2016-12-07 | GSE90953 | GEO
Project description:Background: Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. Methods: An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Results: We determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. Patients on statin treatment showed higher diabetes prevalence (OR=2.67; 95%CI, 1.60-4.45; P= 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein-1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism. Conclusions: DNL gene activation profile in response to statins was associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.
2019-05-15 | GSE130991 | GEO