Metabolic features of the tumor microenvironment of gastric cancer and the link to the systemic macroenvironment
Metabolic features of the tumor microenvironment of gastric cancer and the link to the systemic macroenvironment
复制标题
DOI：
10.1007/s11306-011-0297-0
复制
发表时间：
2012-02-01
期刊：
影响因子：
3.6
通讯作者：
Wang, Guangji
中科院分区：
文献类型：
--
作者：
Aa, Jiye;Yu, Lianzhen;Wang, Guangji
局部肿瘤对整个系统的代谢影响以及肿瘤微环境与全身宏观环境之间的联系知之甚少。在这项研究中，我们分析了组织和血浆中的代谢产物收集胃癌（GC）患者，术后GC患者和对照组慢性浅表性胃炎（CSG）患者。GC患者的组织和血浆显示出与CSG对照组明显不同的代谢表型。显著升高的糖酵解，三羧酸循环（TCA），和氨基酸周转的GC组织的代谢特征;和更大的代谢扰动中观察到GC组织比GC血浆中，无论是与对照组相比。值得注意的是，在组织和血浆中，表征GC的区别性代谢物的水平不呈正相关。例如，TCA中间体、乳酸盐、氨基酸和游离脂肪酸在组织中更丰富，但在血浆中相对于CSG对照浓度较低;而GC患者的组织和血浆中的葡萄糖均低于对照。我们首次显示了肿瘤微环境和全身环境之间代谢物的平衡概况。此外，手术切除胃癌组织后，胃癌患者的上述分子水平在不同程度上得到恢复，表明全身环境与肿瘤微环境的关系。结果进一步表明，完整组织的代谢组学分析是一种潜在的替代技术，用于GC的临床诊断。
The metabolic effects of local tumors on the whole system and the link between the tumor microenvironment and the systemic macroenvironment are poorly known. In this study, we profiled the metabolites in tissues and plasma collected from patients with gastric cancer (GC), postoperative GC patients, and control patients with chronic superficial gastritis (CSG). The tissues and plasma of the GC patients showed distinctly different metabolic phenotypes from those of the CSG controls. Significantly elevated glycolysis, tricarboxylic acid cycle (TCA), and amino acids turnover characterized metabolism of GC tissues; and greater metabolic perturbation were observed in GC tissues than that in GC plasma, both compared with the controls. Remarkably, the levels of the discriminatory metabolites characterizing GC were not positively correlated in tissues and plasmas. For examples, TCA intermediates, lactate, amino acids and free fatty acids were more abundant in the tissues but less concentrated in plasma relative to their CSG controls; while glucose was lower in both the tissues and plasma of GC patients than the controls. For the first time we showed a balance profile of metabolites between tumor microenvironment and the systemic environment. Additionally, the surgical removal of the GC tissue restored the levels of the molecules cited above to different extent in postoperative GC patients, indicating the relationship of systemic environment to tumor microenvironment. The results further suggested that metabolomic analysis of intact tissues is potentially an alternative technique for the clinical diagnosis of GC.