Abstract
BackgroundLong noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are also reportedly involved in regulating glycolysis metabolism. However, glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in cancers.MethodsGlycolysis scores and glycolysis-associated lncRNA signatures were established using a single-sample gene set enrichment analysis (GSEA) of The Cancer Genome Atlas pan-cancer data. Consensus clustering assays and genomic classifiers were used to stratify patient subtypes and for validation. Fisher’s exact test was performed to investigate genomic mutations and molecular subtypes. A differentially expressed gene analysis, with GSEA, transcription factor (TF) activity scoring, cellular distributions, and immune cell infiltration, was conducted to explore the functions of glycolysis-associated lncRNAs.ResultsGlycolysis-associated lncRNA signatures across 33 cancer types were generated and used to stratify patients into distinct clusters. Patients in cluster 3 had high glycolysis scores and poor survival, especially in bladder carcinoma, low-grade gliomas, mesotheliomas, pancreatic adenocarcinomas, and uveal melanomas. The clinical significance of lncRNA-defined groups was validated using external datasets and genomic classifiers. Gene mutations, molecular subtypes associated with poor prognoses, TFs, oncogenic signaling such as the epithelial-to-mesenchymal transition (EMT), and high immune cell infiltration demonstrated significant associations with cluster 3 patients. Furthermore, five lncRNAs, namely MIR4435-2HG, AC078846.1, AL157392.3, AP001273.1, and RAD51-AS1, exhibited significant correlations with glycolysis across the five cancers. Except MIR4435-2HG, the lncRNAs were distributed in nuclei. MIR4435-2HG was connected to glycolysis, EMT, and immune infiltrations in cancers.ConclusionsWe identified a subgroup of cancer patients stratified by glycolysis-associated lncRNAs with poor prognoses, high immune infiltration, and EMT activation, thus providing new directions for cancer therapy.
Highlights
Long noncodingRNAs and glycolysis are both recognized as key regulators of cancers
We identified a subgroup of cancer patients stratified by glycolysis-associated Long noncoding RNA (lncRNA) with poor prognoses, high immune infiltration, and epithelial-to-mesenchymal transition (EMT) activation, providing new directions for cancer therapy
By performing the Pearson correlation analysis, we identified 1420 lncRNA candidates that were associated with glycolytic activity in at least one cancer type
Summary
Long noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are reportedly involved in regulating glycolysis metabolism. Glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in cancers. A wellestablished metabolic pathway that plays a prominent role in cancer progression is glycolysis, which is critical for supplying energy and producing metabolic end products, maintaining tumor cell survival [2]. In addition to its functions in sustaining tumor growth, activation of glycolysis affects other phenotypic changes. Lactic acid produced by the glycolysis pathways induces the epithelial-to-mesenchymal transition (EMT) in lung cancer cells [3]. A pan-cancer study reported that activated glycolysis is correlated with increasing tumor immunity [4]. Understanding the underlying relationship between glycolysis and cancer progression is a critical goal in cancer research
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