Methylation and transcriptome analysis reveal lung adenocarcinoma-specific diagnostic biomarkers

Abstract

Background: DNA 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. Methods: Differentially 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. Results: A 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. Conclusions: Methylation-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.