Identification of subgroups and development of prognostic risk models along the glycolysis-cholesterol synthesis axis in lung adenocarcinoma

Background Lung cancer is one of the most dangerous malignant tumors affecting human health. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Both glycolytic and cholesterogenic pathways play critical roles in metabolic adaptation to cancer. Methods A dataset of 585 LUAD samples was downloaded from The Cancer Genome Atlas (TCGA) database. We obtained co-expressed glycolysis and cholesterogenesis genes by selecting and clustering genes from Molecular Signatures Database v7.5. Compared the prognosis of different subtypes and identified differentially expressed genes (DEGs) between subtypes. Predictive outcome events were modeled using machine learning, and the top 9 most important prognostic genes were selected by Shapley additive explanation (SHAP) analysis. A risk score model was built based on multivariate Cox analysis. Results LUAD patients were categorized into four metabolic subgroups: cholesterogenic, glycolytic, quiescent, and mixed. The worst prognosis was the mixed subtype. The prognostic model had great predictive performance in the test set. Conclusions Patients with LUAD were effectively typed by glycolytic and cholesterogenic genes and were identified as having the worst prognosis in the glycolytic and cholesterogenic enriched gene groups. The prognostic model can provide an essential basis for clinicians to predict clinical outcomes for patients. ### Competing Interest Statement The authors have declared no competing interest.