Background: The heterogeneity of lung adenocarcinoma (LADC) makes the early diagnosis and treatment of the disease difficult. Gene silencing of DNA methylation is an important mechanism of tumorigenesis. A combination of methylation and clinical features can improve the classification of LADC heterogeneity.

Results: We investigated the prognostic significance of 335 specimen subgroups of Lung adenocarcinoma based on the DNA methylation level. The differences in DNA methylation levels were related to the TNM stage classification, age, gender, and prognostic values. Seven subtypes were determined using 774 CpG sites that significantly affected the survival rate based on the consensus clustering. Finally, we constructed a prognostic model that performed well and further verified it in our test group.

Conclusions: This study shows that classification based on DNA methylation might aid in demonstrating heterogeneity within formerly characterized LADC molecular subtypes, assisting in the development of efficient, personalized therapy.

Methods: Methylation data of lung adenocarcinoma were downloaded from the University of California Santa Cruz (UCSC) cancer browser, and the clinical patient information and RNA-seq archives were acquired from the Cancer Genome Atlas (TCGA). CpG sites were identified based on the significant correlation with the prognosis and used further to cluster the cases uniformly into several subtypes.