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.