基于代谢组学的胃癌组织和血浆的糖代谢研究

摘要

背景:肿瘤细胞糖酵解明显增强,但糖酵解对机体全身代谢的影响尚不明确.目的:研究胃癌患者组织和血浆的糖代谢中间产物变化,以建立胃癌局部代谢与机体全身代谢的联系.方法:收集20份慢性胃炎组织、17份胃癌组织、15份慢性胃炎血浆、15份胃癌血浆和15份胃癌术后血浆样本,应用气相色谱-飞行时间质谱(GC-TOFMS)方法检测糖代谢中间产物的变化.结果:共鉴定出13种糖代谢中间产物.与慢性胃炎组织相比,胃癌组织中麦芽糖、葡萄糖、甲基β-D-吡喃葡萄糖苷、6-磷酸果糖、核糖浓度明显降低而乳糖、乳酸、柠檬酸浓度明显升高(P＜0.05).与慢性胃炎血浆相比,胃癌血浆葡萄糖、乳酸、琥珀酸、延胡索酸和苹果酸浓度明显降低而蔗糖、甲基β-D-吡喃葡萄糖苷浓度明显升高(P＜0.05).与胃癌血浆相比,胃癌术后血浆蔗糖、半乳糖酸内酯、甲基β-D-吡喃葡萄糖苷浓度明显降低而葡萄糖、乳酸、柠檬酸、琥珀酸、延胡索酸、苹果酸明显升高(P＜0.05).结论:胃癌组织存在糖酵解、三羧酸循环代谢异常,并对全身代谢产生了影响.基于GC-TOFMS的代谢组学是研究胃癌代谢轮廓的合适平台.%Clycolysis is significantly elevated in tumor cells, but the effect of glycolysis on systemic metabolism is still unclear. Aims: To investigate the changes of saccharometabolism intermediates in tissues and plasma of patients with gastric cancer (GC) in order to establish the link between local metabolism of tumor and systemic metabolism. Methods: Eighty-two samples including 20 chronic superficial gastritis (CSG) tissue samples, 17 GC tissue samples, 15 CSG plasma samples, IS GC plasma samples and IS postoperative GC plasma samples were collected. Changes of saccharometabolism intermediates were detected by gas chromatography-time of flight mass spectrometry (GC-TOFMS) technique. Results: A total of 13 saccharometabolism intermediates were identified. Compared with CSG tissues, maltose, glucose, methyl β-D-glucopyranoside, fructose-6-phosphate and ribose decreased significantly while lactose, lactic acid and citric acid increased significantly in GC tissues (P<0.05). Compared with CSG plasma, glucose, lactic acid, succinic acid, fumaric acid and malic acid decreased significantly while sucrose and methyl β-D-glucopyranoside increased significantly in GC plasma (P<0.05). Compared with GC plasma, sucrose, L-galactono-l,4-lactone and methyl P-D-glucopyranoside decreased significantly while glucose, lactic acid, citric acid, succinic acid, fumaric acid and malic acid increased significantly in postoperative GC plasma (P<0.05). Conclusions: This study demonstrates that there is a metabolic dysregulation of glycolysis and tricarboxylic acid cycle in GC tissues, and it affects the systemic metabolism. GC-TOFMS-based metabolomics can be used as a suitable method for studying the metabolism of GC.