Comprehensive Analysis to Reveal Amino Acid Metabolism-Associated Genes as a Prognostic Index in Gastric Cancer.

ABSTRACT

Background: Amino acid metabolism (AAM) is related to tumor growth, prognosis, and therapeutic response. Tumor cells use more amino acids with less synthetic energy than normal cells for rapid proliferation. However, the possible significance of AAM-related genes in the tumor microenvironment (TME) is poorly understood. Methods: Gastric cancer (GC) patients were classified into molecular subtypes by consensus clustering analysis using AAMs genes. AAM pattern, transcriptional patterns, prognosis, and TME in distinct molecular subtypes were systematically investigated. AAM gene score was built by least absolute shrinkage and selection operator (Lasso) regression. Results: The study revealed that copy number variation (CNV) changes were prevalent in selected AAM-related genes, and most of these genes exhibited a high frequency of CNV deletion. Three molecular subtypes (clusters A, B, and C) were developed based on 99 AAM genes, which cluster B had better prognosis outcome. We developed a scoring system (AAM score) based on 4 AAM gene expressions to measure the AAM patterns of each patient. Importantly, we constructed a survival probability prediction nomogram. The AAM score was substantially associated with the index of cancer stem cells and sensitivity to chemotherapy intervention. Conclusion: Overall, we detected prognostic AAM features in GC patients, which may help define TME characteristics and explore more effective treatment approaches.