标题：Methylation and transcriptome analysis reveal lung adenocarcinoma-specific diagnostic biomarkers
作者：Li, Rui; Yang, Yi-E; Yin, Yun-Hong; Zhang, Meng-Yu; Li, Hao; Qu, Yi-Qing
作者机构：[Li, Rui; Yin, Yun-Hong; Zhang, Meng-Yu; Li, Hao; Qu, Yi-Qing] Shandong Univ, Dept Resp & Crit Care Med, Qilu Hosp, Jinan 250012, Shandong, Peoples R 更多
通讯作者：Li, H;Qu, YQ
通讯作者地址：[Li, H; Qu, YQ]Shandong Univ, Dept Resp & Crit Care Med, Qilu Hosp, Jinan 250012, Shandong, Peoples R China.
来源：JOURNAL OF TRANSLATIONAL MEDICINE
关键词：Lung adenocarcinoma; Methylation-driven lncRNA; Methylation-driven mRNA;; Biomarkers; Overall survival rate
摘要：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.