Dataset Information

The seAFOod (Systematic Evaluation of Aspirin and Fish Oil) polyp prevention trial and STOP-ADENOMA (STudy Of Prevention by Aspirin anD EPA; kNowledge Of Mechanism of Action) sub-study

ABSTRACT: Currently as of 29/05/2019: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-aspirin-and-fish-oil-possible-way-preventing-small-growths-forming-bowel-seafood Previously: http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-aspirin-and-fish-oil-possible-way-preventing-small-growths-forming-bowel-seafood

DISEASE(S): Oral And Gastrointestinal Colon,Bowel Cancer,Colorectal Adenoma (polyp),Oral And Gastrointestinal Colorectal Cancer,Gastrointestinal

PROVIDER: 2407543 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA). Objectives: To characterize the transcriptomic and metabolomic profiles of NIUA patients undergoing aspirin desensitization. Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were separated from the blood of NIUA patients undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to mRNA- and lncRNA-seq. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semi-targeted metabolomics panel. Results: Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of pre- versus post-desensitization and healthy control versus post-desensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from pre-aspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, post-dose and pre-dose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in pre-aspirin desensitization samples. Interleukin (IL)-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in pre-aspirin desensitization patients compared to controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of pre-aspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in pre-aspirin desensitization patients compared to healthy controls. Conclusion: This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way towards a molecular diagnosis of NSAID hypersensitivity.

Dataset Information

The seAFOod (Systematic Evaluation of Aspirin and Fish Oil) polyp prevention trial and STOP-ADENOMA (STudy Of Prevention by Aspirin anD EPA; kNowledge Of Mechanism of Action) sub-study

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