Arginine is a protective factor for risk and prognosis of gastric cancer: an observational and Mendelian randomization study.

BACKGROUND: Previous research has indicated that certain amino acids possess anti-tumor properties. However, the impact of blood amino acid levels on the risk of gastric cancer remains uncertain, and a comprehensive analysis examining the association between blood amino acids and the prognosis of gastric cancer is lacking. METHODS: We performed a Mendelian randomization analysis to explore the link between 22 blood amino acids and gastric cancer risk. We also assessed how these amino acids affect gastric cancer prognosis using Cox regression analyses and visualized this with Kaplan-Meier survival curves. A nomogram prognostic model was developed, and its predictive value was evaluated using ROC curves. Additionally, we examined the effects of a key amino acid on cell proliferation and gene expression in gastric cancer cells through CCK-8 assays and transcriptomic sequencing, followed by GO and KEGG pathway analyses to understand the molecular regulation of responsive genes. RESULTS: Our study revealed a significant negative correlation between arginine levels and the risk of gastric cancer. Moreover, only arginine emerged as an independent prognostic factor for gastric cancer, regardless of age, sex, stage, differentiation, and other amino acids. Furthermore, the nomogram prognostic model, incorporating arginine, sex, age, differentiation, and stage, demonstrated a robust prognostic ability. The area under the curve (AUC) for predicting 1-year, and 3-year survival rates were 0.949 and 0.962, respectively. The CCK-8 analysis showed that higher arginine levels inhibited gastric cancer cell growth. Additionally, GO and KEGG enrichment profiling revealed that the identified DEGs were primarily involved in metabolism pathway and protein-binding function. CONCLUSION: Arginine is a protective factor for the risk and prognosis of gastric cancer.