P036 Analysis of intestinal tissue from newly diagnosed patients with inflammatory bowel disease reveals distinct proteomic profiles

Abstract Background Inflammatory bowel disease (IBD) is a complex multi-factorial characterized by chronic inflammation of the gastrointestinal tract. Despite significant efforts to understand pathogenetic mechanisms IBD, elucidation its etiopathology and progression far from fully understood. The direct analysis intestinal tissue endoscopy which leads IBD diagnosis (before starting any treatment) would be ideal sample elucidate pathogenesis. Methods High-throughput mass-spectrometry-based quantitative proteomic was performed using formalin-fixed paraffin-embedded human samples newly diagnosed patients potential responsible for gut in Crohn′s (CD) ulcerative colitis (UC). For this purpose, 192 40 active UC patients, 67 CD 46 normal biopsies healthy controls (HC) were analyzed (Figure 1). Proteins with p-value < 0.05 considered as significantly dysregulated. Moreover, we used Ingenuity Pathway Analysis (IPA) analyze pathways functions different locations (ileum or left colon) that could related Results A total 2,903 proteins identified, 1,010 differentially expressed between colon HC. 1,242 HC, 952 differential discriminated patients. In comparative study ileum Crohn's controls, 956 2). IPA revealed multiple canonical pathways, including EIF2 signaling, regulation eIF4 serine/threonine kinase P7056K mitochondrial dysfunction, oxidative phosphorylation altered compared HC 3). Regarding samples, main enrichment comparison following: neutrophil extracellular trap signaling fatty acid oxidation, sirtuin pathway, tRNA charging, dysfunction 4). Conclusion results dysregulated may unravel key contributing pathogenesis these diseases. serve point hypotheses search therapeutic targets.