Immune, metabolic landscapes of prognostic signatures for lung adenocarcinoma based on a novel deep learning framework

Abstract

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor with high lethality, and the aim of this study was to identify promising biomarkers for LUAD. Using the TCGA-LUAD dataset as a discovery cohort, a novel joint framework VAEjMLP based on variational autoencoder (VAE) and multilayer perceptron (MLP) was proposed. And the Shapley Additive Explanations (SHAP) method was introduced to evaluate the contribution of feature genes to the classification decision, which helped us to develop a biologically meaningful biomarker potential scoring algorithm. Nineteen potential biomarkers for LUAD were identified, which were involved in the regulation of immune and metabolic functions in LUAD. A prognostic risk model for LUAD was constructed by the biomarkers HLA-DRB1, SCGB1A1, and HLA-DRB5 screened by Cox regression analysis, dividing the patients into high-risk and low-risk groups. The prognostic risk model was validated with external datasets. The low-risk group was characterized by enrichment of immune pathways and higher immune infiltration compared to the high-risk group. While, the high-risk group was accompanied by an increase in metabolic pathway activity. There were significant differences between the high- and low-risk groups in metabolic reprogramming of aerobic glycolysis, amino acids, and lipids, as well as in angiogenic activity, epithelial-mesenchymal transition, tumorigenic cytokines, and inflammatory response. Furthermore, high-risk patients were more sensitive to Afatinib, Gefitinib, and Gemcitabine as predicted by the pRRophetic algorithm. This study provides prognostic signatures capable of revealing the immune and metabolic landscapes for LUAD, and may shed light on the identification of other cancer biomarkers.