Genes associate with Immunity and Amino Acid Metabolism in Lung adenocarcinoma (LUAD): A bioinformatic analysis
Authors: Zhang Yuxin , Wang Yuehui , Zhang Ruoxuan , Li Quanwang 
Published: September 2023

Background
Lung adenocarcinoma (LUAD) represents the most prevalent subtype of primary lung cancer. Amino acids play a vital role as essential nutrients for both tumor cells and immune cells. Both tumor cells and immune cells exhibit specific and distinctive amino arequirements. Many tumors overexpress enzymes that degrade amino acids, which provide energy and metabolites for anabolic processes and also act as a mechanism for immune evasion of cancells. Thus, an in-depth exploration of the relationship between immunity and amino acid metabolism in LUAD is crucial. The identification of stable and reliable tumor markers can facilitate patient screening for poor prognosis, leading to more aggressive treatment approaches.
Methods
This study utilized 539 LUAD samples and 59 normal samples obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes ( between LUAD and normal tissue were identified through analysis of processed expression profile data. The study focused on genes associated with immune response and amino acid metabolism among the differentially expressed genes. Subsequently, potential mechanisms, biological characteristics, and pathways related to LUAD were investigated in the cancer and normal groups using Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA). A prognostic model was then established through LASSO-COX analysis, considering risk scores and prognostic factors to identify markers influencing the occurrence and prognosis of LUAD.
Results
Differential expression analysis identified 377 genes at the intersection of up-regulated differentially expressed genes and Amino Acid Metabolism-related genes (AAMGs). Protein-protein interaction (PPI) analysis on these 377 genes, associated with immunity and amino acid metabolism, yielded 17 hub genes selected based on top 30 scores from five algorithms. A LASSO regression analysis-based prognosis model was constructed to evaluate the prognostic value of these 17 hub genes using the TCGA-LUAD dataset. Validation with a combined dataset confirmed four genes, polo-like kinase(PLK1), Ribonucleotide Reductase Subunit M2 (RRM2), Thyroid Hormone Receptor Interactor 13 (TRIP13), and Hyaluronan-Mediated Motility Receptor (HHMR), as consistent results in the TCGA-LUAD dataset. The accuracy of the model was further verified through ROC curve analysis and the COX model. Additionally, immunohistochemical analysis of PLK1 expression in LUAD tumor tissue and normal thyroid tissue from the HPA database, using antibody HPA053229, showed higher PLK1 expression levels in LUAD tumor tissue.
Conclusion
LUAD development is strongly associated with immunity and amino acid metabolism. Four genes, namely, PLK1, RRM2, TRIP13, and HMMR, hold prognostic value for lung adenocarcinoma. High expression of PLK1 in LUAD may contribute to tumorigenesis by regulating the cell cycle and could serve as a prognostic indicator for clinical outcomes.