Abnormal arginine metabolism is associated with prognosis in patients of gastric cancer

Abstract

Background: Metabolic disorder is a key factor in the occurrence and development of tumors. Metabolomics methods can explore a variety of prognostic markers for tumors. Methods: The 454 patients included in this study comprised 92 cases of gastric cancer, 51 cases of gastric ulcers, 206 cases of gastric polyps, and 105 cases of gastritis. The plasma levels of 23 amino acids in patients before treatment were detected by liquid chromatography-tandem mass spectrometry, and t-test was used to determine the difference of amino acids levels between the gastric cancer group and other groups. Shared different amino acids were selected to analyze their relationship with staging, differentiation and prognosis. The TCGA database was used to explore the changes of genes expression related to the synthesis and degradation of different amino acids, and the relationship between the genes and stage, differentiation and prognosis. Results: The plasma arginine level in the gastric cancer group was significantly higher than that in the gastric ulcer, gastric polyp, and gastritis groups (P values 0.0065, 0.0306, 0.0004, respectively).The level of plasma arginine in patients with non-metastatic gastric cancer was significantly higher than that in patients with metastatic gastric cancer (P=0.0013). Compared with the normal control, the key metabolic enzyme ASS1 gene was highly expressed in gastric cancer, and the survival time of gastric cancer patients with high expression of ASS1 was longer. Patients with high arginine expression had significantly longer survival (log-rank test P=0.0003). Conclusions: Increased plasma arginine level in gastric cancer patients was related to overexpression of ASS1 by TCGA database analysis. High expression of ASS1 prolonged the overall survival of gastric cancer patients, and the arginine level before treatment could be used as a prognostic factor.