Construction of lung adenocarcinoma subtype and prognosis model based on fatty acid metabolism-related genes.

Objective: To explore the role of genes related to fatty acid metabolism in lung adenocarcinoma classification and prognosis.

Methods: Transcriptome and clinical data from the TCGA database and GEO database were collected, the expression of prognostic fatty acid metabolism-related genes in LUAD patients was analyzed, and key genes related to both fatty acid metabolism and subtype were identified. These key genes were further filtered via the LASSO regression method, and the retained genes were used to construct a risk-scoring model. The biological function of RPS4Y1 was verified by cell viability, colony formation, migration, and flow cytometry assays. Finally, immune infiltration and drug sensitivity were analyzed in the high- and low-risk groups.

Results: 31 key FAMGs associated with prognosis were identified in LUAD patients. LUAD cases were divided into 3 subtypes on the basis of the expression of these genes. The DEGs between the different subtypes were associated mainly with amino acid metabolic pathways. In addition, among the 46 DEGs between subtypes, 5 key FAMGs (SCGB3 A2, PGC, ADH7, RPS4Y1, and KRT6 A) were identified as the best prognostic markers via LASSO regression to establish a risk scoring model. Patients with low risk scores had a better prognosis and a greater degree of immune cell infiltration than those with high risk scores. RPS4Y1 is highly expressed in LUAD, and its knockdown significantly inhibits the growth of tumor cells. Moreover, we also analyzed drugs likely to be effective for the high- and low-risk groups.

Conclusion: FAMGs play important roles in LUAD, and the key genes identified may be new targets for LUAD treatment.