Comprehensive Analysis of Subtypes and Identification of Key lncRNAs Based on Glutamine Metabolism-Related Long Noncoding RNAs.

Abstract

Background Long noncoding RNAs (lncRNAs) are becoming a critical class of metabolic regulate molecule in cancer. Glutamine is a regulator that contributes to each of the core metabolic tasks in proliferating tumor cells. Thus, we aimed to evaluate the association of lncRNAs with glutamine metabolism in lung adenocarcinoma (LUAD). Methods Using single-sample gene set enrichment analysis (ssGSEA), LUAD specimens were assigned scores based on glutamine metabolism-related genes, and the shared common glutamine metabolism-related lncRNAs in three different LUAD data cohorts were identified. ConsensusClusterPlus was used to perform unsupervised clustering analysis in patients with LUAD. Key glutamine metabolism-related lncRNAs were identified by first-order partial correlation analysis. Results A total of 11 shared glutamine metabolism-associated lncRNAs were identified in three LUAD data cohorts, and LUAD patients were classified into three glutamine metabolism subtypes based on the expressions of the related genes. C1 exhibited shorter overall survival (OS), poor genomic instability, and inadequate infiltration of immune cell types in the tumor microenvironment (TME) and was representative of the immunodeficiency phenotype. C2 represented the immunosuppressive phenotype while C3 represented the immune activation phenotype, exhibiting the highest sensitivity to immunotherapy. Nine of the 11 lncRNAs were localized to the nucleus. Finally, three key lncRNAs, significantly enriched in multiple metabolic pathways, were screened and found to be remarkably related to the OS of LUAD. Conclusion We identified three glutamine metabolism subtypes of LUAD, which reflected different OS, genomic, and TME features, and identified three key glutamine metabolism-associated lncRNAs may contribute to further study of lncRNAs in cancer metabolism.