Multi-omics analysis-based clinical and functional significance of a novel prognostic and immunotherapeutic gene signature derived from amino acid metabolism pathways in lung adenocarcinoma.

Background: Studies have shown that tumor cell amino acid metabolism is closely associated with lung adenocarcinoma (LUAD) development and progression. However, the comprehensive multi-omics features and clinical impact of the expression of genes associated with amino acid metabolism in the LUAD tumor microenvironment (TME) are yet to be fully understood. Methods: LUAD patients from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort. Using least absolute shrinkage and selection operator Cox regression analysis, we developed PTAAMG-Sig, a signature based on the expression of tumor-specific amino acid metabolism genes associated with overall survival (OS) prognosis. We evaluated its predictive performance for OS and thoroughly explored the effects of the PTAAMG-Sig risk score on the TME. The risk score was validated in two Gene Expression Omnibus (GEO) cohorts and further investigated against an original cohort of chemotherapy combined with immune checkpoint inhibitors (ICIs). Somatic mutation, chemotherapy response, immunotherapy response, gene set variation, gene set enrichment, immune infiltration, and plasma-free amino acids (PFAAs) profile analyses were performed to identify the underlying multi-omics features. Results: TCGA datasets based PTAAMG-Sig model consisting of nine genes, Conclusion: In patients with LUAD, the PTAAMG-Sig effectively predicted OS, drug sensitivity, and immunotherapy outcomes. These findings are expected to provide new targets and strategies for personalized treatment of LUAD patients.