Abstract
BackgroundDNA methylation can regulate the role of long noncoding RNAs (lncRNAs) in the development of lung adenocarcinoma (LUAD). The present study aimed to identify methylation-driven lncRNAs and mRNAs as biomarkers in the prognosis of LUAD using bioinformatics analysis.MethodsDifferentially expressed RNAs were obtained using the edge R package from 535 LUAD tissues and 59 adjacent non-LUAD tissues. Differentially methylated genes were obtained using the limma R package from 475 LUAD tissues and 32 adjacent non-LUAD tissues. Methylation-driven mRNA and lncRNA were obtained using the MethylMix R package from 465 LUAD tissues with matched DNA methylation and RNA expression and 32 non-LUAD tissues with DNA methylation. Gene ontology and ConsensusPathDB pathway analysis were performed to identify functional enrichment of methylation-driven mRNAs. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of each variable for predicting the prognosis of LUAD. Kaplan–Meier curve analysis of DNA methylation and gene expression might provide potential prognostic biomarkers for LUAD patients.ResultsA total of 99 methylation-driven mRNAs and 17 methylation-driven lncRNAs were obtained. Univariate and multivariate Cox regression analysis showed that 6 lncRNAs (FOXE1, HOXB13-AS1_2, VMO1, HIST1H3F, AJ003147.8, ASXL3) were retrieved to construct a predictive model associated with overall survival in LUAD patients. Combined DNA methylation and gene expression survival analysis revealed that 4 lncRNAs (AC023824.1, AF186192.1, LINC01354 and WASIR2) and 8 mRNAs (S1PR1, CCDC181, F2RL1, EFS, KLHDC9, MPV17L, GKN2, ITPRIPL1) might act as independent biomarkers for the prognosis of LUAD.ConclusionsMethylation-driven lncRNA and mRNA contribute to the survival of LUAD, and 4 lncRNAs and 8 mRNAs might be potential biomarkers for the prognosis of LUAD.
Highlights
DNA methylation can regulate the role of long noncoding RNAs in the development of lung adenocarcinoma (LUAD)
A large number of studies have demonstrated that DNA methylation can regulate the expression of long noncoding RNAs (lncRNAs), and this phenomenon may be associated with the prognosis of lung cancer [15]
Identification of methylation‐driven mRNA and lncRNA in LUAD A total of 99 mRNAs and 17 lncRNAs were identified to be associated with DNA methylation using MethylMix criteria
Summary
DNA methylation can regulate the role of long noncoding RNAs (lncRNAs) in the development of lung adenocarcinoma (LUAD). DNA methylation acts as the key element in epigenetic modifications and plays a significant role in the regulation of cellular functions and carcinogenesis [7,8,9]. Epigenetic modification, especially DNA methylation, Li et al J Transl Med (2019) 17:324 can provide a novel horizon to explore new biomarkers in predicting the prognosis of cancer [10,11,12,13,14]. A large number of studies have demonstrated that DNA methylation can regulate the expression of lncRNA, and this phenomenon may be associated with the prognosis of lung cancer [15]. The lncRNA AFAP1-AS1 acts as an oncogene in NSCLC, while its expression is tightly regulated by DNA methylation, which might provide prognostic and diagnostic values for NSCLC patients [16]
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