Metabolic features of the tumor microenvironment of gastric cancer and the link to the systemic macroenvironment

Abstract

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.

A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine

“…The effect of berberine on lipid metabolism, gut flora and the turnover of bile acids may play an important role in elucidating the lipid lowering effect of berberine. Metabolomics provides an ideal platform to characterize metabolic patterns involved in perturbation of physiology by various stimuli, either genetic 14 , or environmental alternation, such as food 15 and xenobiotic drugs or toxins 16 , and further to explore underlying mechanism and elucidate biomarkers in different levels, such as systematic/body, local/organs and cellular levels 17-20 . Considering that hamsters are an excellent hyperlipidemic model 21 , in this study, we employed metabolomics, used a high-fat diet (HFD)-induced hyperlipidemic hamster model to examine whether the lipid-lowering effect of berberine is associated with metabolism of lipids and the turnover of bile acids.…”

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

“…Nine studies investigated esophageal cancer (39-47), 3 gastric cancer (48)(49)(50), and 15 colorectal cancer (29,30,(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). Two studies investigated more than one GI malignancy (64,65).…”

Review of Mass Spectrometry–Based Metabolomics in Cancer Research

“…Myo-inositol, which was increased in various types of cancers (48, 64, 100), might provide a link to the phosphoinositide-3-kinase (PI3K) pathway in cancer. This indicates that well known cancer pathways, such as PI3K, not only show their effects in the proteome, but also in the metabolome.…”