Bile Metabolites and Risk of Carcinogenesis in Patients With Pancreaticobiliary Maljunction: A Pilot Study
Bile Metabolites and Risk of Carcinogenesis in Patients With Pancreaticobiliary Maljunction: A Pilot Study
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DOI：
10.21873/anticanres.14779
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发表时间：
2021-01-01
影响因子：
2
通讯作者：
Shimada, Mitsuo
中科院分区：
文献类型：
--
作者：
Mori, Hiroki;Morine, Yuji;Shimada, Mitsuo
背景/目的：胰胆功能障碍（PBM）是一种胰胆内胆汁反流的疾病，是胆道癌的高危因素。本研究的目的是通过对手术期间采集的胆汁进行代谢组学分析，探讨PBM的致癌机制。患者和方法：三名PBM无胆道癌患者，四名肝外胆管癌（EHBC）患者，和三名良性疾病的对照。采用毛细管电泳-质谱法和液相色谱-质谱法对胆汁样品进行代谢组学分析，以区分氨基酸和脂质组学谱。结果如下：主成分分析显示PBM患者和EHBC患者的代谢产物相似;此外，PBM和EHBC患者与对照组相比存在明显差异。氨基酸谱揭示了PBM的以下20种潜在致癌候选物：异亮氨酸、苯丙氨酸、酪氨酸、亮氨酸、色氨酸、精氨酸、赖氨酸、缬氨酸、天冬酰胺、甲硫氨酸、天冬氨酸、丝氨酸、苏氨酸、组氨酸、谷氨酰胺、丙氨酸、脯氨酸、谷氨酸和谷氨酸。脂质组学特征揭示了以下11种致癌候选物：溶血磷脂酰胆碱、溶血磷脂酰乙醇胺、磷脂酰甘油、溶血磷脂酰甘油、三酰甘油、二酰甘油、神经酰胺、鞘磷脂、脂肪酸、贯叶金丝桃素和维生素D。在这些特征性代谢物中，已知支链氨基酸、甲硫氨酸和溶血磷脂酰胆碱与致癌作用有关。结论：PBM和EHBC患者胆汁代谢产物极其相似。此外，与健康对照组相比，PBM或EHBC患者的氨基酸和脂质代谢明显不同。
Background/Aim: Pancreaticobiliary malfunction (PBM), a disease with reflux of pancreatic and bile juice in the pancreaticobiliary tract, is a high-risk factor for biliary tract cancer. The aim of this study was to investigate the mechanism of carcinogenesis in PBM using a metabolomics analysis of bile sampled during surgery. Patients and Methods: Three patients with PBM without biliary tract cancer, four patients with extrahepatic bile duct cancer (EHBC), and three controls with benign disease were enrolled. Metabolomics analysis of bile samples was performed using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to discriminate the amino acid and lipidomic profiles. Results: The principal component analysis in the capillary electrophoresismass spectrometry and liquid chromatography-mass spectrometry revealed similar metabolites in patients with PBM and those with EHBC; furthermore, there was a clear difference between patients with PBM or EHBC compared to controls. The amino acid profiles revealed the following 20 potential carcinogenic candidates for PBM: isoleucine, phenylalanine, tyrosine, leucine, tryptophan, arginine, lysine, valine, asparagine, methionine, aspartic acid, serine, threonine, histidine, glutamine, alanine, proline, glutamic acid, and pyruvic acid. The lipidomic profiles revealed the following 11 carcinogenic candidates: lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidyl glycerol, lysophosphatidyl glycerol, triacylglycerol, diacylglycerol, ceramide, sphyngomyeline, fatty acid, hyperforin, and vitamin D. Among these characteristic metabolites, the branched-chain amino acids, methionine and lysophosphatidylcholine are known to be related to carcinogenesis. Conclusion: The bile metabolites were extremely similar in patients with PBM and those with EHBC. Furthermore, amino acid and lipid metabolism was markedly different in patients with PBM or EHBC compared to healthy controls.