Understanding the Critical Role of Glycolysis-Related LncRNAs in Lung Adenocarcinoma Based on Three Molecular Subtypes

Background: Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy.

Methods: Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance.

Results: Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis.

Conclusions: This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.