Liang Han, Deng Jianlian, Luo Tian, Luo Huijuan, Li Fuqiang, Wu Kui, Lin Cong
HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou 310000, China.
Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen 518083, China.
Heliyon. 2024 Dec 6;10(24):e41006. doi: 10.1016/j.heliyon.2024.e41006. eCollection 2024 Dec 30.
Considerable differences in molecular characteristics have been defined between non-smoker and smokers in patients with lung adenocarcinoma (LUAD), yet studies on open chromatin patterns associated with LUAD progression caused by smoking are still lacking. Here, we 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, and pathway analysis was conducted to identify potential pathways involved. We identified a set of peaks that discriminated smokers in LUAD patients according to levels of exposure to tobacco quantified in pack-years. These peaks were also significantly associated with progression-free survival and overall survival of these patients. Further examination of the gene set related to those peaks revealed that the comprising genes, such as , and are strongly associated with LUAD development. They are consistent with the important roles of the associated pathways in LUAD oncogenesis induced by smoking, including estrogen response, apical junction and glycolysis pathways. In summary, our study may provide valuable insights into exploring ATAC-seq peaks and understanding smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.
在肺腺癌（LUAD）患者中，已明确非吸烟者和吸烟者之间存在显著的分子特征差异，但关于吸烟导致LUAD进展的开放染色质模式的研究仍然缺乏。在此，我们使用我们先前开发的算法，基于来自TCGA数据的每个ATAC-seq峰之间的相关性构建了一个新的网络。随后，对通过相关网络过滤保留峰的LUAD样本进行主成分分析，并进行通路分析以确定涉及的潜在通路。我们根据以包年量化的烟草暴露水平，确定了一组能够区分LUAD患者中吸烟者的峰。这些峰也与这些患者的无进展生存期和总生存期显著相关。对与这些峰相关的基因集的进一步检查表明，所包含的基因，如 、 和 与LUAD的发展密切相关。它们与吸烟诱导的LUAD肿瘤发生中相关通路的重要作用一致，包括雌激素反应、顶端连接和糖酵解通路。总之，我们的研究可能为从开放染色质变化的角度探索ATAC-seq峰和理解吸烟相关的LUAD致癌作用提供有价值的见解。
