Abstract 4P
Background
Lung carcinoma is one of the most prevalent and life-threatening cancers globally, with tobacco smoking being the most significant cause of lung cancer deaths. Lung adenocarcinoma (LUAD) accounts for approximately 80-85% of reported lung cancer cases and unfolds in a sequential multistage pattern, gradually developing genetic and epigenetic alterations. Alterations in DNA methylation at CpG sites are associated with smoking-induced lung cancer. Smoking-related epigenetic alterations are involved in the modulation of multiple biological pathways. Enhancers govern gene expression across great distances by looping DNA and offering distant regulatory regions closer to their target gene promoters.
Methods
Therefore, we employed Illumina HM450k DNA methylation data of patients from The Cancer Genome Atlas (TCGA) to determine enhancers and link enhancer status with the expression of target genes to discover transcriptional targets using The Enhancer Linking by Methylation/Expression Relationship (ELMER). In this study, we investigated a technique for predicting enhancer-target interactions by combining epigenomic and transcriptomic data from primary tumor samples.
Results
This approach allowed us to identify target genes specifically regulated by enhancers with differential methylation patterns in LUAD and revealed the target genes of the differentially methylated sites and the enriched motifs modulating their expression in LUAD progression playing a key role as central regulators of ribosome biogenesis, RNA processing, and dysregulated mitochondrial ribosomal proteins, impacting mitochondrial translation, oxidative phosphorylation.
Conclusions
Our study illuminates the landscape of LUAD progression, intricately shaped by smoking-induced genetic and epigenetic alterations. Using enhancer-target interactions through advanced analyses of DNA methylation data, we uncovered specific transcriptional targets influenced by differential methylation patterns, which allowed us to identify key hub genes central to critical pathways. This comprehensive approach enhances our understanding of LUAD pathogenesis, providing potential avenues for targeted therapeutic interventions.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.