Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

Abstract

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

Discriminating gastric cancer and gastric ulcer using human plasma amino acid metabolic profile

“…Miyagi et al observed that citrulline, valine, tryptophan and histidine levels were significantly lower in GC patient plasma, whereas isoleucine and lysine were higher . Song et al demonstrated that plasma glutamine level decreased in GC patients . Our study generated similar results that GC patients had lower glutamine, histidine, arginine and tryptophan levels and higher ornithine concentration.…”

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).…”

Determination of Urinary 5-Hydroxyindoleacetic Acid as a Metabolomics in Gastric Cancer

“…Measuring the serum level of tumor markers (VEGF, IL-6), oxidative stress markers (Nitric oxide, MDA) [20], gastric mucosal secretary markers (Gastrin-17, Pepsinogen I [21], and Eicosanoids (prostaglandins, leukotriene) [22] are among these studies. Profiling metabolites in the serum and urine of gastric cancer patients revealed a total of 18 and 7 biomolecules (including carbohydrates, amino acids, fatty acids, and steroids) with a significant difference in comparison with the serum and urine of normal individuals, respectively [23][24][25]. Among these metabolic fingerprints, amino acids take a particular part.…”

“…Among these metabolic fingerprints, amino acids take a particular part. While the serum levels of glutamine is depleted due to increased consumption of this metabolite, the serum level of valin is increased due to possible increase in valin catabolism by cancer cells [23]. On the other hand, there is a significant decline in the urinary level of L-serin and L-threonin due to participation of these two amines in glycolysis or Tri carboxylic acid (TCA) cycle [25].…”