Abstract (Master Thesis)

Aberrant DNA methylation accompanied by aberrant gene expression is a hallmark feature of many cancer types, including lung cancer. To investigate how these events are associated and what disease-associated pathways are under epigenetic regulation, we perform genome-wide expression-methylation Quantitative Trait Loci (emQTL) analysis by integrating DNA methylation and gene expression data obtained from lung adenocarcinoma (LUAD) patients. Grouping emQTLs through biclustering led to the discovery of biological pathways associated with immune cell infiltration, proliferation, and hormone signaling. Of particular interest, we found the hormone-related CpGs to be enriched in enhancer regions and the binding sites for transcription factors linked to hormone-related signaling such as FOXA1 /2, FOSL1/2, SMAD3, and JUN. The identified hormone-related genes and CpGs were connected through chromatin interaction loops, implying the implication of DNA methylation in epigenetic regulation through enhancer-promoter interactions. Moreover, by performing unsupervised hierarchical clustering of the emQTL-genes and CpGs, we identify and validate subclasses of patients with different prognoses based on the expression pattern of hormone-related genes. The identified molecular subclasses partially overlapped with known molecular subtypes in LUAD, providing additional information in tumor classification not captured by previous studies using transcriptomic data independently from DNA methylome.