Development and validation of a survival model for lung adenocarcinoma based on autophagy-associated genes

BACKGROUND: Given that abnormal autophagy is involved in the pathogenesis of cancers, we sought to explore the potential value of autophagy-associated genes in lung adenocarcinoma (LUAD). METHODS: RNA sequencing and clinical data on tumour and normal samples were acquired from The Cancer Genome Atlas (TCGA) database and randomly assigned to training and testing groups. Differentially expressed autophagy-associated genes (AAGs) were screened. Within the training group, Cox regression and Lasso regression analyses were conducted to screen five prognostic AAGs, which were used to develop a model. Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves were plotted to determine the performance of the model in both groups. Immunohistochemistry was used to demonstrate the differential expression of AAGs in tumour and normal tissues at the protein level. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to further elucidate the roles of AAGs in LUAD. RESULTS: The data from the TCGA database included 497 tumour and 54 normal samples, within which 30 differentially expressed AAGs were screened. Using Cox regression and Lasso regression analyses for the training group, 5 prognostic AAGs were identified and the prognostic model was constructed. Patients with low risk had better overall survival (OS) in the training group (3-year OS, 73.0% vs 48.0%; 5-year OS, 45.0% vs 33.8%; P = 1.305E−04) and in the testing group (3-year OS, 66.8% vs 41.2%; 5-year OS, 31.7% vs 25.8%; P = 1.027E−03). The areas under the ROC curves (AUC) were significant for both the training and testing groups (3-year AUC, 0.810 vs 0.894; 5-year AUC, 0.792 vs 0.749). CONCLUSIONS: We developed a survival model for LUAD and validated the performance of the model, which may provide superior outcomes for the patients.