Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235569 | GEO | 2023/06/27
REPOSITORIES: GEO
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Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD DNA obtained from 164 AERD subjects, 397 subjects with aspirin-tolerant asthma (ATA), 398 normal controls and 10 null samples were subjected to Exome Chip assay of 240K SNPs. 1023 model (210-1) were generated from combination of the top 10 SNPs selected by p-values. The area under the curve (AUC) value of receiver operating characteristic (ROC) curves was calculated for each model. SNP functional Portal and PolyPhen-2 was used to validate the functional significance of the candidate SNPs
2014-09-05 | E-GEOD-61129 | biostudies-arrayexpress
Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD
2014-09-05 | GSE61129 | GEO
Project description:Aspirin-exacerbated respiratory disease (AERD) has association with severe asthma and aspirin can cause asthma to worsen, often in the form of a severe and sudden attack. The oral aspirin challenge (OAC) is the gold standard to confirm the diagnosis of AERD but it is time consuming and produces serious complications in some cases. Therefore more efficient and practical method is needed to predict AERD patients. The aim of the present study was to identify AERD-related gene expression in peripheral blood mononuclear cells (PBMCs) and examine the diagnostic potential of these candidate gene(s) for predicting AERD. To do this, RNAs from 24 subjects with AERD and 18 subjects with aspirin-tolerant asthma (ATA) were subjected to microarray analysis of ~34,560 genes. In total, 10 genes were selected as candidate gene markers by applying p ≤ 0.001(t-test) and ≥ 8-fold change and to correct for multiple comparisons, the false discovery rate (FDR) analyses were performed. By applying multiple logistic regression analysis, among possible 1023 models (210–1), a model consisting of CNKSR3, SPTBN2, and IMPACT was selected as candidate set, because this set showed the best AUC (0.98) with 88% sensitivity and 89% specificity. For validation, mRNA levels by real-time PCR on PBMCs from two population sets in a gene-chip study and another replication sample: 20 AERD, 20 ATA, and 8 normal controls, were significantly different between groups with 100% sensitivity and 100% specificity in each of the two population sets. However, IMPACT gene didn’t differentiate between AERD and normal controls. The set of the two genes (CNKSR3 and SPTBN2) showed the best AUC (0.96) with 88% sensitivity and 94% specificity in a gene chip study sample. In addition, this set showed perfect discriminative power with AUC (1.0, 100% sensitivity and 100% specificity) in each of the two population sets: the gene-chip samples and the replication samples. It also showed perfect discrimination for AERD form NC (AUC 1.0) and ATA from NC (AUC 1.0). In conclusion, we developed the two gene markers (CNKSR3 and SPTBN2) of PBMC which differentiate between AERD and ATA with a perfect discriminative power. These gene markers may be an efficient and practical method useful for predicting AERD. Total 24 AERD (Aspirin-exacerbated respiratory disease) and 18 ATA(aspirin-tolerant asthma) samples were used to find bio-markers using 35K op-array.
2013-04-08 | E-GEOD-45847 | biostudies-arrayexpress
Project description:Aspirin-exacerbated respiratory disease (AERD) has association with severe asthma and aspirin can cause asthma to worsen, often in the form of a severe and sudden attack. The oral aspirin challenge (OAC) is the gold standard to confirm the diagnosis of AERD but it is time consuming and produces serious complications in some cases. Therefore more efficient and practical method is needed to predict AERD patients. The aim of the present study was to identify AERD-related gene expression in peripheral blood mononuclear cells (PBMCs) and examine the diagnostic potential of these candidate gene(s) for predicting AERD. To do this, RNAs from 24 subjects with AERD and 18 subjects with aspirin-tolerant asthma (ATA) were subjected to microarray analysis of ~34,560 genes. In total, 10 genes were selected as candidate gene markers by applying p ≤ 0.001(t-test) and ≥ 8-fold change and to correct for multiple comparisons, the false discovery rate (FDR) analyses were performed. By applying multiple logistic regression analysis, among possible 1023 models (210–1), a model consisting of CNKSR3, SPTBN2, and IMPACT was selected as candidate set, because this set showed the best AUC (0.98) with 88% sensitivity and 89% specificity. For validation, mRNA levels by real-time PCR on PBMCs from two population sets in a gene-chip study and another replication sample: 20 AERD, 20 ATA, and 8 normal controls, were significantly different between groups with 100% sensitivity and 100% specificity in each of the two population sets. However, IMPACT gene didn’t differentiate between AERD and normal controls. The set of the two genes (CNKSR3 and SPTBN2) showed the best AUC (0.96) with 88% sensitivity and 94% specificity in a gene chip study sample. In addition, this set showed perfect discriminative power with AUC (1.0, 100% sensitivity and 100% specificity) in each of the two population sets: the gene-chip samples and the replication samples. It also showed perfect discrimination for AERD form NC (AUC 1.0) and ATA from NC (AUC 1.0). In conclusion, we developed the two gene markers (CNKSR3 and SPTBN2) of PBMC which differentiate between AERD and ATA with a perfect discriminative power. These gene markers may be an efficient and practical method useful for predicting AERD.
2013-04-08 | GSE45847 | GEO
Project description:Aspirin is a non-steroidal anti-inflammatory drug. Till date there is no information on the molecular mechanism of aspirin on oral cancer cells. In this study, treated oral cancer cells were compared with untreated ones for gene expression for finding the effect of aspirin on biological process and significant pathways involved. Aspirin plays an important role in inducing apoptotic effect by activating regulators and further inhibits cell cycle progression.
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2019-03-05 | PXD003655 | Pride
Project description:STOX1 overexpressing placentas generate preeclampsia-like symptoms in pregnant mice. These symptoms are reverted by aspirin. The experiment aims at analyzing placental expression in Transgenic/non transgenic with and withou aspirin, in the placentas at 16,5 days post-coïtum. There are two strains of transgenic mice that express the transgene at different levels: STOX42 about 15 fold that of STOX13. STOX13 expressed the human STOX1 roughly at the level of the mouse endogeneous Stox1 in the placenta.
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Project description:Aspirin, is a commonly used non-steroidal anti-inflammatory drug with antipyretic, analgesic, anti-inflammatory, and anti-thrombotic effect. Its antitumoral effect was also demonstrated in several cancer types. In this study our aim was to investigate the genomic effects of ASA in pituitary adenomas using high-throughput profiling approaches and validate our findings by targeted methodologies, using in vitro functional assays. Whole transcriptome profile of RC4-B/C and GH3 pituitary cell lines upon Aspirin treatment was investigated.
2022-06-19 | GSE202934 | GEO
Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to speculation that aspirin-mediated lysine acetylation could explain some of its drug actions or side-effects. Using a labeled form of aspirin, aspirin-d3, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies acetylation signals at thousands of sites, cells tolerate aspirin mediated acetylation very well unless endogenous deacetylases are inhibited. Apart from a limited number of cellular proteins that are substantially acetylated under endogenous conditions, aspirin mediated acetylation leads to a large increase in the acetylation of many proteins even although they remain at very low stoichiometry. This reinforces the idea that a major function of cellular deacetylases is the suppression of non-specific or non-enzymatic protein acetylation.
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