N-6 methylation-related lncRNA is potential signature in lung adenocarcinoma and influences tumor microenvironment.
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ABSTRACT: Background
N-6 methylation (m6A) pushes forward an immense influence on the occurrence and development of lung adenocarcinoma (LUAD). However, the methylation on non-coding RNA in LUAD, especially long non-coding RNA (lncRNA), has not been received sufficient attention.Methods
Spearman correlation analysis was used to screen lncRNA correlated with m6A regulators expression from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, respectively. Then, the least absolute shrinkage and selection operator (LASSO) was applied to build a risk signature consisting m6A-related lncRNA. Univariate and multivariate independent prognostic analysis were applied to evaluate the performance of signature in predicting patients' survival. Next, we applied Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to conduct pathway enrichment analysis of 3344 different expression genes (DEGs). Finally, we set up a competing endogenous RNAs (ceRNA) network to this lncRNA.Results
A total of 85 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by LASSO regression contained 11 lncRNAs: ARHGEF26-AS1, COLCA1, CRNDE, DLGAP1-AS2, FENDRR, LINC00968, TMPO-AS1, TRG-AS1, MGC32805, RPARP-AS1, and TBX5-AS1. M6A-related lncRNA risk score could predict the prognostic of LUAD and was significantly associated with clinical pathological. And in the evaluation of lung adenocarcinoma tumor microenvironment (TME) by using ESTIMATE algorithm, we found a statistically significant correlation between risk score and stromal/immune cells.Conclusion
M6A-related lncRNA was a potential prognostic and therapy target for lung adenocarcinoma.
SUBMITTER: Zheng J
PROVIDER: S-EPMC8605119 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most fatal cancers in the world. Previous studies have shown the increase in glycosylation level, and abnormal expressions of related enzymes are closely related to various cancers. Long non-coding RNAs (lncRNAs) play an important role in the proliferation, metabolism, and migration of cancer cells, but the underlying role of glycosyltransferase (GT)-related lncRNAs in LUAD remains to be elucidated.MethodsWe abstracted 14,056 lncRNAs from The Cancer Genome Atlas (TCGA) dataset and 257 GT-related genes from the Gene Set Enrichment Analysis (GSEA) database. Univariate, LASSO-penalized, and multivariate Cox regression analyses were conducted to construct a GT-related lncRNA prognosis model.ResultsA total of 2,726 GT-related lncRNAs were identified through Pearson's correlation analysis, and eight of them were utilized to construct a GT-related lncRNA model. The overall survival (OS) of the low-risk group continued to be superior to that of the high-risk group according to the subgroups classified by clinical features. The risk model was proved to have independent prognostic characteristics for LUAD by univariate and multivariate Cox regression analyses. The status of the tumor immune microenvironment and the relevant immunotherapy response was significantly different between the two risk groups. The candidate drugs aimed at LUAD subtype differentiation were identified.ConclusionWe constructed a risk model comprising eight GT-related lncRNAs which was identified as an independent predictor of prognoses to predict patient survival and guide-related treatments for patients with LUAD.
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