Epigenome-Wide Tobacco-Related Methylation Signature Identification and Their Multilevel Regulatory Network Inference...

Area of Science:

• Genomics
• Epigenetics
• Oncology

Background:

• Tobacco exposure is a primary risk factor for lung cancer, but its molecular mechanisms remain largely unknown.
• DNA methylation plays a significant role in regulating gene expression in cancer cells.
• Understanding tobacco-related epigenetic alterations is key to deciphering lung cancer development.

Purpose of the Study:

• To identify tobacco-related DNA methylation signatures in lung adenocarcinoma (LUAD).
• To analyze the regulatory networks of these signatures at gene and protein levels.
• To explore potential therapeutic targets for LUAD based on these findings.

Main Methods:

• Utilized three independent LUAD datasets for model training and validation.
• Employed a deep selecting method to identify methylation signature probes from whole epigenome data.
• Applied BIMC, SRC, and shortest path tracing for gene association analysis, alongside KEGG and GO enrichment analyses.

Main Results:

• Identified 105 tobacco-related DNA methylation signature probes associated with 95 genes.
• Discovered 33 highly related genes at the gene regulation level, including hub genes like FARSB.
• Uncovered core genes in the protein-protein interaction network, such as MAGOH and FYN.

Conclusions:

• The identified DNA methylation signatures provide insights into the molecular mechanisms of tobacco-induced lung tumorigenesis.
• These signatures may serve as valuable biomarkers for classifying tobacco exposure patterns in LUAD.
• The identified genes and pathways represent potential targets for precision medicine interventions in LUAD.