Construction and validation of a prognostic model for stemness-related genes in lung adenocarcinoma.

ABSTRACT

Background: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with poor overall prognosis. Early identification of high-risk patients and individualized treatment can help extend the survival time of patients. This study aimed to construct and validate a prognostic prediction least absolute shrinkage and selection operator (LASSO) model for stemness-related genes in LUAD. Methods: Firstly, LUAD RNA-sequencing data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor stemness index based on mRNA expression (mRNAsi) was calculated, and the relationship between mRNAsi and the survival prognosis as well as clinical features of LUAD patients was analyzed. Then, the weighted gene co-expression network analysis (WGCNA) method was used to screen for gene modules highly correlated with mRNAsi, and functional annotation [Gene Ontology (GO) analysis] and pathway enrichment analysis [Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis] were performed for the selected stemness-related gene module. Furthermore, prognosis-associated genes were determined from the stemness-related genes through univariate Cox analysis, and a prognostic model was constructed using LASSO analysis. Finally, a series of validations including survival curve analysis, receiver operating characteristic (ROC) curve analysis, and risk analysis were conducted for the prognostic model, and nomogram based on the risk model and various clinicopathological features were constructed. Results: LUAD patients with high mRNAsi had a higher mortality rate than those with low mRNAsi. GO analysis showed that stemness-related genes were mainly involved in mRNA processing and extracellular matrix organization, while KEGG analysis revealed their involvement in cell cycle and PI3K-Akt signaling pathways. A prognostic model based on 12 stemness-related genes was constructed using LASSO regression. Validation of the prognostic model demonstrated its good accuracy in predicting the prognosis of LUAD patients. Conclusions: mRNAsi plays an important role in the occurrence and development of LUAD. This study successfully constructed a prognostic prediction LASSO model for stemness-related genes in LUAD, which can serve as a novel prognostic indicator for LUAD and may be an effective complement to the current Tumor Node Metastasis (TNM) clinical staging of LUAD.