Our results for creQTL from the Gene Ontology enrichment analysis indicated a regulatory hierarchy, consistent with data from wet-lab studies, where signal transduction molecules receive signals at the plasma membrane and transduce them through various intracellular intermediates to the nucleus to activate specific transcription factors, other DNA-binding proteins, and other transcriptional regulatory proteins. The relative abundances of DNA-binding proteins at the promoter region may control gene expression [43]. Because of the enrichment of cell adhesion and signaling ontologies at the cell junction and membrane at the highest significance levels, the major steps of gene regulation in endometrial cancer may occur not within the nucleus but rather at the cellular membrane. In addition, GO enrichment in genes required for telomere maintenance suggests additional target genes and loci for further investigation, as telomerase has long been considered an attractive target for therapy in endometrial carcinoma [44] and more recently, a mouse model of endometrial cancer showed that telomere length affected initiation of type II carcinogenesis [45].
