Identification of metabolism-related gene signature in lung adenocarcinoma

Lung cancer is one of the most common cancers in China and has a high mortality rate. Most patients who are diagnosed have lost the opportunity to undergo surgery. Aberrant metabolism is closely associated with tumorigenesis. We aimed to identify an effective metabolism-related prediction model for assessing prognosis based on the cancer genome atlas (TCGA) and GSE116959 databases.

TCGA and GSE116959 datasets from Gene Expression Omnibus were used to obtain lung adenocarcinoma (LUAD) data. Additionally, we captured metabolism-related genes (MRGs) from the GeneCards database. First, we extracted differentially expressed genes using R to analyze the LUAD data. We then selected the same differentially expressed genes, including 168 downregulated and 77 upregulated genes. Finally, 218 differentially expressed MRGs (DEMRGs) were included to perform functional enrichment analysis and construct a protein-protein interaction network with the help of Cytoscape and Search Tool for the Retrieval of Interacting Genes database. Cytoscape was used to visualize the intensive intervals in the network. Then univariate and Least Absolute Shrinkage and Selection Operator Cox regression analyses, which assisted in identifying the overall survival (OS)-related DEMRGs and building a 10-DEMRG prognosis model, were performed. The prognostic values, tumor immunity relevance, and molecular mechanism were further investigated. A nomogram incorporating signature, age, gender, and TNM stage was established.

A 10-DEMRG model was established to forecast the OS of LUAD through Least Absolute Shrinkage and Selection Operator regression analysis. This prognostic signature stratified LUAD patients into low-risk and high-risk groups. The receiver operating characteristic curve and K-M analysis indicated good performance of the DEMRGs signature at predicting OS in the TCGA dataset. Univariate and multivariate Cox regression also revealed that the DEMRGs signature was an independent prognosis factor in LUAD. We noticed that the risk score was substantially related to the clinical parameters of LUAD patients, covering age and stage. Immune analysis results showed that risk score was associated with some immune cells and immune checkpoints. Nomogram also verified the clinical value of the DEMRGs signature.

In this study, we constructed a DEMRGs signature and established a prognostic nomogram that is robust and reliable to predict OS in LUAD. Overall, the findings could help with therapeutic customization and personalized therapies.