Carneiro Tatiana J, Pinto Joana, Serrao Eva M, Barros António S, Brindle Kevin M, Gil Ana M
CICECO - Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Aveiro, Portugal.
Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
Front Mol Biosci. 2022 Aug 25;9:937865. doi: 10.3389/fmolb.2022.937865. eCollection 2022.
Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation.
利用核磁共振（NMR）代谢组学方法，对蛙皮素诱导的胰腺炎小鼠模型（Pt）和胰腺癌转基因小鼠模型（PCa）胰腺的极性提取物进行非靶向分析，以寻找胰腺炎的代谢标志物，并描述胰腺癌进展过程中的代谢变化。通过多变量分析，发现了一种特定于Pt组织的10种代谢物的代谢特征，可将良性状态与正常组织和癌前组织（低级别胰腺上皮内瘤变，PanIN，病变）区分开来。小鼠胰腺在从正常组织，经低级别和高级别PanIN病变发展到胰腺导管腺癌（PDA）的过程中表现出显著变化。这些变化包括乳酸生成增加、与增强的回补反应一致的氨基酸变化、膜生物合成中间体（磷酸胆碱和磷酸乙醇胺）浓度降低以及糖基化尿苷磷酸降低，反映了己糖胺生物合成途径和蛋白质糖基化的激活。
