Development of Amino Acid Metabolism-Related Prognostic Model and Immune Infiltration Analysis in Patients with Stomach Adenocarcinoma

Abstract

Abstract Stomach adenocarcinoma (STAD) is a major contributor to cancer mortality worldwide. Alterations in amino acid metabolism have been reported in various tumors. However, the prognostic value of amino acid metabolism-related genes in STAD deserves to be further elucidated. In this study, we constructed a prognostic risk model consisting of 3 amino acid metabolism-related genes (SERPINE1, NRP1, MATN3) in STAD. Based on the median risk score, STAD patients were divided into high- and low-risk groups. The patients with high-risk scores had a worse prognosis. A nomogram consisting of risk score and various clinical characteristics accurately predicted the 1-, 3-, and 5-year survival time of STAD patients. Notably, KEGG pathway enrichment analysis indicated immune-related pathways enriched in the high-risk group. High-risk scores were significantly related to C6 (TGF-β dominant type), while low-risk scores were significantly related to C4 (lymphocyte-depleted type). The higher risk score was associated with higher immune infiltration, immune-related function, lower tumor purity and worse response to immunotherapy. In addition, the model genes were correlated with antitumor drug sensitivity. Finally, functional assays confirmed that interference of model gene MATN3 inhibited the proliferation and migration of STAD cells. In conclusion, the amino acid metabolism-related prognostic model might be used as a biomarker to predict the prognosis and guide immunotherapy for STAD patients.