Prognostic Implication of Energy Metabolism-Related Gene Signatures in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is the major non-small-cell lung cancer pathological subtype with poor prognosis worldwide. Herein, we aimed to build an energy metabolism-associated prognostic gene signature to predict patient survival.

The gene expression profiles of patients with LUAD were downloaded from the TCGA and GEO databases, and energy metabolism (EM)-related genes were downloaded from the GeneCards database. Univariate Cox and LASSO analyses were performed to identify the prognostic EM-associated gene signatures. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. A CIBERSORT analysis was used to evaluate the correlation between the risk model and immune cells. A nomogram was used to predict the survival probability of LUAD based on a risk model.

We constructed a prognostic signature comprising 13 EM-related genes (AGER, AHSG, ALDH2, CIDEC, CYP17A1, FBP1, GNB3, GZMB, IGFBP1, SORD, SOX2, TRH and TYMS). The Kaplan-Meier curves validated the good predictive ability of the prognostic signature in TCGA AND two GEO datasets (p<0.0001, p=0.00021, and p=0.0034, respectively). The area under the curve (AUC) of the ROC curves also validated the predictive accuracy of the risk model. We built a nomogram to predict the survival probability of LUAD, and the calibration curves showed good predictive ability. Finally, a functional analysis also unveiled the different immune statuses between the two different risk groups.

Our study constructed and verified a novel EM-related prognostic gene signature that could improve the individualized prediction of survival probability in LUAD.