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.

Prognostic value of lncRNAs related to fatty acid metabolism in lung adenocarcinoma and their correlation with tumor microenvironment based on bioinformatics analysis

“…Energy metabolism pathways, such as the pentose phosphate pathway, are abundant in the high-risk group. Liu et al ( 58 ) discovered that LUAD patients with a poor prognosis are predominantly enriched in the pentose phosphate pathway, which is consistent with the findings of the current investigation. Moreover, unlike protein-coding genes, the majority of pentose phosphate-related lncRNAs were negatively correlated with pentose phosphate activity and were linked with a poor prognosis ( 59 , 60 ).…”

Comprehensive analysis of Major depression Related gene Signature for predicting prognosis in lung adenocarcinoma

“…This pathway is highly related to TCA cycle, which is very important for the proliferation and apoptosis of cancer cells. In addition, the relationship between pentose phosphate pathway and cancer progression has been widely studied [41] , and related lncRNA has been reported as an important prognostic marker in LUAD [42] . Corresponding to the highrisk group, Glycosaminoglycan biosynthesis-hyperparan sulfate/heparin, Nitrogen metabolism, Vitamin B6 metabolism and other pathways are High expression in low-NeuScore type cells.…”

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

“…TP53-induced glycolysis is the main apoptosis regulator (TIGAR) in PPP [ 174 ]. MicroRNA (miR)-218 (miR-218) reduced glucose consumption in NSCLC through PPP [ 175 ]. PPP-related lncRNAs for NSCLC has an improved detection and treatment based on the different upregulated immune checkpoints in C1 subtype [ 176 ].…”