糖尿病患者结直肠癌代谢组学的研究

目的 研究糖尿病患者结直肠癌组织代谢组学的改变。方法 采用气液相质谱仪(GC-MS)检测15例糖尿病结直肠癌患者的肿瘤和癌旁相邻正常组织的代谢谱的变化。结果 总共检测出有334种生化分子,结直肠癌组织样品和其匹配的健康邻近组织相比代谢状况发生了显著的变化。肿瘤组织中,葡萄糖、3-磷酸甘油酸和磷酸烯醇式丙酮酸含量显著下降(P<0.01),乳酸含量增加,糖代谢中瓦氏效应明显。用于肿瘤合成的嘌呤、嘧啶及其中间产物水平显著上调。甘油脂代谢中,甘油和甘油-3-磷酸的含量降低。结直肠癌组织中,β-丙氨酸、GPG、泛酸增加。结论 在糖尿病患者结直肠癌组织中,包括糖代谢等多种代谢通路发生了代谢重排。不常见的代谢物变化将来也许可以应用于结直肠癌的早期发现和治疗。
Objective To study on the changes of tissue metabolomics in diabetic patients with colorectal cancer. Methods The metabolomic profiles of the tumor tissue and adjacent normal tissue samples from 15 diabetic patients with colorectal cancer were studied by gas chromatography-mass spectrometry (GC-MS). Results Three hundred and thirty four biochemical molecules were detected. The metabolic status of the colorectal cancer tissue was significantly altered compared with that of adjacent normal tissue. Metabolomic profiling revealed that tumor tissue samples expressed lower levels of glucose, 3-phosphoglycerate, and phosphoenolpyruvate (PEP) compared to adjacent normal tissue, with a corresponding increase in lactate production, showing an obvious Warberg effect in the glycometabolism. A strong upregulation of key intermediates in both purine and pyrimidine synthesis was observed and there was also a shift in glycerolipid metabolism with a noted decrease in glycerol and glycerol-3-phosphate. The levels of β-alanine,GPG (glycerophosphoglycerate) and pantothenate were increased in tumor tissue compared to control samples. Conclusion Metabolicderangements in the colorectal cancer tissue including alterations in many of metabolic pathways provide a constant supply to support metabolic demands for abnormal tumor growth and development. Such unique oncometabolites will help to evaluate in the early detection and treatment of colorectal cancer