A novel CpG island methylation panel predicts survival in lung adenocarcinomas.

Abstract

The lack of clinically useful biomarkers compromise the personalized management of lung adenocarcinomas (ADCs); epigenetic events and DNA methylation in particular have exhibited potential value as biomarkers. By comparing genome-wide DNA methylation data of paired lung ADCs and normal tissues from 6 public datasets, cancer-specific CpG island (CGI) methylation changes were identified with a pre-specified criterion. Correlations between DNA methylation and expression data for each gene were assessed by Pearson correlation analysis. A prognostically relevant CGI methylation signature was constructed by risk-score analysis, and was validated using a training-validation approach. Survival data were analyzed by log-rank test and Cox regression model. In total, 134 lung ADC-specific CGI CpGs were identified, among which, a panel of 9 CGI loci were selected as prognostic candidates, and were used to construct a risk-score signature. The novel CGI methylation signature was identified to classify distinct prognostic subgroups across different datasets, and was demonstrated to be a potent independent prognostic factor for overall survival time of patients with lung ADCs. In addition, it was identified that cancer-specific CGI hypomethylation of RPL39L, along with the corresponding gene expression, provided optimized prognostication of lung ADCs. In summary, cancer-specific CGI methylation aberrations are optimal candidates for novel biomarkers of lung ADCs; the 9-CpG methylation panel and hypomethylation of RPL39L exhibited particularly promising significance.