Identification of Two Subtypes and Prognostic Characteristics of Lung Adenocarcinoma Based on Pentose Phosphate Metabolic Pathway-Related Long Non-coding RNAs

Abstract

This study analyzed the differences in subtypes and characteristics of advanced lung adenocarcinoma (LUAD) patients based on the pentose phosphate metabolic pathway-related long non-coding RNAs (lncRNAs), along with their potential regulatory mechanisms. Using the expression profiling and corresponding clinical information of LUAD patients from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Differential pathway scores between normal and tumor samples from TCGA were identified by rank-sum tests. Pearson correlation coefficients between pentose phosphate scores of the pentose phosphate samples and lncRNAs of the corresponding datasets were calculated. Next, the clusterProfiler software package was used for functional annotation. Clustering of pentose phosphate-related lncRNAs from LUAD samples categorized two molecular subtypes (C1, and C2). C1 was associated with a lower pentose phosphate score and a good prognosis; the C2 showed a higher pentose phosphate score and was related to poorer prognoses. The C2 was markedly associated with energy metabolic pathways. The expression of most immune cells were markedly higher in C1 subtype. Some crucial immune checkpoints, including CTLA4, CD274, and CD47, were also significantly upregulated in C1 subtype, leading to a higher score of clinical effect on the C1 subtype. Finally, one TF, BACH1, was found to be significantly upregulated in C1 subtypes; the pathways activated by this TF may be associated with tumor progression and poor prognoses. LUAD typing based on pentose phosphate metabolic pathway-related lncRNAs was confirmed. Differences in characteristics between C1 and C2 subtypes improved the current LUAD detection and treatment.