The critical role of histone modifications in lung adenocarcinoma based on novel molecular subtypes.

Abstract

e20510 Background: Studies revealed the pathogenesis and exploring the treatment of lung adenocarcinoma (LUAD), but overall survival (OS) of LUAD patients still remains low in the recent years. Methods: This study analyzed the relationship between gene expression and histone modifications, and discussed the prognostic value of these findings in patients with LUAD. Four types of histone modifications including H3K9me3, H3K27me3, H3K27ac and H3K4me3 were included. Promoters and enhancers in protein coding genes (PCGs) were selected as targeted analyzing regions. Unsupervised consensus clustering was performed to identify molecular subtypes. Cox regression analysis and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model. Results: A large number of epigenetic abnormal genes in lung adenocarcinoma were found by comparing the histone modifications and methylation regions on the elements including. We identified 699 epigenetic dysregulated genes specific to LUAD. Finally, based on these epi-PCGs, we constructed three molecular types of LUAD and identified 5 epi-PCGs as prognostic markers for LUAD patients. Conclusions: Our research provided a better understanding that the abnormal epigenetic regulation of PCG expression contributes a lot for the progress of gene regulation in LUAD. These novel molecular subtypes and the prognostic model could serve as guiders to assist decision-makings for LUAD treatment.