Targeted metabolomic profiling of gastric cancer biopsies

Background and objectives Gastric cancer, the fifth most diagnosed malignancy worldwide and seventh in India, exhibits high metabolic activity and marked heterogeneity. In this study, we performed targeted metabolomic profiling of gastric cancer biopsies obtained through esophagogastroduodenoscopy in a South Indian cohort. Methods Targeted metabolite profiling was conducted using liquid chromatography-mass spectrometry (LC-MS) analysis. Pathway enrichment and biomarker evaluation were performed using MetaboAnalyst 6.0, incorporating univariate analysis and receiver operating characteristic (ROC) curve assessment. Results LC-MS based analysis of tumour (n=25), paired normal (n=25), and normal gastric mucosa (n=3) samples revealed distinct metabolic alterations associated with gastric cancer. The metabolic profiles of tumours and paired normal tissues were similar when compared with normal mucosa, suggesting a potential field effect in gastric carcinogenesis. A total of 58 metabolites were identified, of which 44.8% comprising peptides, amino acids, and their derivatives showed marked upregulation in tumours, indicating enhanced amino acid metabolism. Elevated uracil and uridine levels suggested altered pyrimidine metabolism, reflecting increased nucleotide turnover and supporting rapid DNA/RNA synthesis. Pathway analysis highlighted modulation of arginine biosynthesis, serine-one carbon metabolism, and nucleotide metabolism in gastric cancer tissues. ROC analysis identified ornithine and citrulline as potential discriminators in gastric cancer. Interpretation and conclusions Our findings reveal differentially altered metabolites in gastric cancer that are predominantly involved in arginine, serine one-carbon, and nucleotide metabolism. Ornithine and citrulline were identified as potential diagnostic biomarkers and therapeutic targets.