Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling
Issued Date
2025-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105000378120
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025)
Suggested Citation
Mukherjee A., Boonbangyang M., K.S M. Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling. Scientific Reports Vol.15 No.1 (2025). doi:10.1038/s41598-025-93769-w Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/108512
Title
Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling
Author(s)
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortalities, characterized by substantial genetic heterogeneity that challenges a comprehensive understanding of its progression. This study employs next-generation sequencing data analysis to transform our comprehension of LUAD pathogenesis. Integrating epigenetic and transcriptomic data of LUAD patients, this approach assessed the critical regulatory occurrences, identified therapeutic targets, and offered profound insights into cancer molecular foundations. We employed the DNA methylation data to identify differentially methylated CpG sites and explored the transcriptome profiles of their adjacent genes. An intersectional analysis of gene expression profiles uncovered 419 differentially expressed genes (DEGs) influenced by smoke-induced differential DNA methylation, among which hub genes, including mitochondrial ribosomal proteins (MRPs), and ribosomal proteins (RPs) such as MRPS15, MRPS5, MRPL33, RPL24, RPL7L1, MRPL15, TUFM, MRPL22, and RSL1D1, were identified using a network-based approach. These hub genes were overexpressed and enriched to RNA processing, ribosome biogenesis, and mitochondrial translation, which is critical in LUAD progression. Enhancer Linking Methylation/Expression Relationship (ELMER) analysis revealed transcription factor (TF) binding motifs, such as JUN, NKX23, FOSB, RUNX3, and FOSL1, which regulated these hub genes through methylation-dependent enhancer dynamics. Predominant hypomethylation of MRPs and RPs disrupted mitochondrial function, contributed to oxidative phosphorylation (OXPHOS) and metabolic reprogramming, favoring cancer cell survival. The survival analysis validated the clinical relevance of these hub genes, with high-expression cohorts exhibiting poor overall survival (OS) outcomes enlightened their relevance in LUAD pathogenesis and presented the potential for developing novel targeted therapeutic strategies.