Multiomics analysis on DNA methylation and the expression of both messenger RNA and microRNA in lung adenocarcinoma

J Cell Physiol. 2019 May;234(5):7579-7586. doi: 10.1002/jcp.27520. Epub 2018 Oct 28.

Abstract

Lung adenocarcinoma (LUAD) poses a significant threat to public health worldwide, while the genetic and epigenetic abnormalities involved in the oncogenesis of LUAD remains unknown. This study aimed to identify and validate key genes during the development and progression of LUAD by multiomics analysis. First, Empirical Analysis of Digital Gene Expression Data in R (EdgeR) was used to identify differentially regulated genes between normal samples and LUAD samples. Then significance analysis of microarrays (SAM) was used to identify differentially methylated genes and regulated microRNAs (miRNAs) between normal samples and LUAD samples. Following that, Kyoto Encyclopedia of Genes and Genomes (KEGG)-enrichment analysis was used to analyze the function that these genes enriched in. A total of 4,816 genes, 419 miRNAs, and 4,476 methylated genes that were significantly differentially expressed corresponding to the normal tissues in LUAD were obtained, and some of the pathways these genes enriched in were the same. Moreover, 255 genes differentially methylated and expressed at the same time were also found, and these 255 genes were the target genes of the miRNAs differentially expressed in LUAD. Finally, nine genes (BRCA1, COL1A1, ESR1, FGFR2, HNF4A, IGFBP3, MET, MMP3, and PAK1) network analysis, and two of which were found to be related to the survival of LUAD patients. In summary, a total of nine genes that may play important roles in the development of LUAD were identified, and two (PAK1 and FGFR2) of them can be served as prognostic biomarkers for LUAD patients. The genes found in this study played different roles in the tumor progression of LUAD, indicating these genes may be considered as potential target genes for LUAD treatment.

Keywords: LUAD; differential expression; differential methylation; multiomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • DNA Methylation / genetics*
  • Disease Progression
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Messenger / genetics*

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger