373P - Chromatin accessibility reveals potential prognostic value of the peak set associated with smoking history in patients with lung adenocarcinoma

Background

Considerable differences in molecular characteristics have been defined between non-smokers and smokers in patients with lung adenocarcinoma (LUAD). However, study of open chromatin patterns associated with LUAD progression caused by smoking is still lacking.

Methods

Here, we firstly constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network. Prognostic value of the significant ATAC-seq peak set with overall survival in these smoking related LUAD patients was assessed. Then, pathway analysis of the peak-related genes was conducted for potential pathways identification.

Results

We identified a set of peaks with significant correlation that clearly differentiated long-term smokers from those with short-term smoking history in LUAD patients and also significantly associated with overall survival of these patients. The gene set that were demonstrated to be related to those peaks, such as B3GNT3, ACTN4 and CLDN3, are strongly associated with LUAD development, which is consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways.

Conclusions

Our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

BGI-Shenzhen, Shenzhen 518083, China.

Funding

Science, Technology, and Innovation Commission of Shenzhen Municipality.

Disclosure

All authors have declared no conflicts of interest.