Development and validation of a metabolic gene signature for predicting the overall survival of patients in lung adenocarcinoma with lymph node metastasis

Abstract

Abstract Purpose Metabolism reprogramming plays an essential role in cancers. The current study explored the prognostic potential of metabolic genes for lung adenocarcinoma (LUAD) with metastasis. Methods The RNA-seq data and clinical data for LUAD patients were retrieved from public databases. LASSO analysis was utilized to construct a multigene signature in the TCGA-LUAD cohort. LUAD patients from the GSE72094, GSE30219, GSE31210 dataset were used for external validation. The effect of altered GNPNAT1 expression on cell migration, invasion and EMT were explored in vitro. Results Our results showed that a total of 40 differentially expressed metabolic genes (DEMGs) were identified to be involved in the occurrence and lymph node metastasis of LUAD. Univariate Cox regression analysis demonstrated that 10 DEMGs were correlated with overall survival (OS) of LUAD patients. LASSO regression analysis indicated that the prognostic signature, including ALDOA, MTHFD1L, LDHA, GNPNAT1, POLR3G, GPD1L, PGS1, was developed in the TCGA-LUAD cohort. The prognostic value of this signature was successfully validated in the GSE72094, GSE31210, GSE30219 dataset. Receiver operating characteristic (ROC) curve analysis confirmed this signature's predictive capacity. Functional analysis revealed that several signaling pathways were enriched in the high-risk group. Furthermore, the calibration curve of the prognostic nomogram demonstrated good agreement between the predicted and observed survival rates for each of OS. Further analysis revealed that this signature could be an independent predictor for OS in patients with LUAD. Finally, we successfully detected expression level of 7 hub MGs at the transcription level and firstly found that GNPNAT1 might played an important role on LUAD cells migration, invasion, and EMT. Conclusion A novel metabolic gene signature can be used for prognostic prediction in LUAD metastasis. Targeting metabolism may be a therapeutic alternative for LUAD metastasis.