Aberrant CpG-methylation affects genes expression predicting survival in lung adenocarcinoma

Cancer Med. 2018 Nov;7(11):5716-5726. doi: 10.1002/cam4.1834. Epub 2018 Oct 23.

Abstract

Lung adenocarcinoma (LUAD) is a common diagnosed disease with high-mortality rate, and its prognostic implications are under discovered. DNA methylation aberrations are not only an important event for dysregulation of gene expression during tumorigenesis but also a revolution in epigenetics by identifying key prognostic biomarkers for multiple cancers. In this study, we analyzed methylation status of 485 578 CpG sites and RNA-seq transcriptomes of 20 532 genes for 1095 LUAD samples in TCGA database. The association between DNA methylation and the prognostic value of the corresponding gene expression was identified as well. In total, ten aberrantly methylated and dysregulated genes (AURKA, BLK, CNTN2, HMGA1, PTTG1, TNS4, DAPK2, MFSD2A, THSD1, and WNT7A) were highlighted which were significantly correlated with overall survival of 492 LUAD patients, which were all reported as tumor-associated genes in other various cancers and worthy of further investigated and might be used as therapeutic targets for LUAD. Together, methylation aberrances regulate gene expression level during tumorigenesis and influence prognosis of LUAD patients. Integrating knowledge of epigenetics and expression of genes can be useful for an in-depth understanding of cancer mechanism and for the eventual purpose of precisely prognostic and therapeutic target verification.

Keywords: RNAseq; lung adenocarcinoma; methylation.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Biomarkers, Tumor / genetics*
  • CpG Islands
  • DNA Methylation*
  • Databases, Genetic
  • Epigenesis, Genetic
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Prognosis
  • Sequence Analysis, RNA
  • Survival Analysis

Substances

  • Biomarkers, Tumor