Differentially Expressed Genes Associated with the Estrogen Receptor Pathway in Cerebral Aneurysms

Background: The pathophysiology of cerebral aneurysm formation remains to be elucidated. Estrogen is thought to be protective against the development of aneurysms. The aim of this study is to identify differentially expressed genes in the estrogen receptor pathway that may be linked to the development of cerebral aneurysms. Methods: Data from 6 Gene Expression Omnibus (GEO) databases with gene expression profiles of cerebral aneurysm tissue were analyzed (GSE6551, GSE15629, GSE26969, GSE46337, GSE54083, and GSE75436). Ninety-four genes associated with the estrogen receptor pathway were identified from the Kyoto Encyclopedia of Genes and Genomes pathway database. A meta-analysis using a random-effects model was used to evaluate the association of the estrogen receptor pathway genes with aneurysm formation. Results: Four genes related to the estrogen receptor pathway were significantly associated with intracranial aneurysms, 2 of which were downregulated (PIK3R1: fold change [FC] = 0.41, false discovery rate [FDR] = 6.1 × 10^–5, ADCY9: FC = 0.55, FDR = 2.3 × 10^–4) and 2 of which were upregulated (HBEGF: FC = 1.46, FDR = 4.9 × 10^–4; ADCY7: FC = 2.11, FDR = 6.0 × 10^–3). Furthermore, subgroup analysis of 2 GEO databases with information provided about sex demonstrated PIK3R1 to be significant independently in both men (FC = 0.46, FDR = 6.3 × 10^–5) and women (FC = 0.46, FDR = 2.3 × 10^–4), whereas JUN, ADCY5, and MMP9 were significant in women only. Conclusions: The analysis of 6 GEO databases revealed 4 differentially expressed genes (PIK3R1, HBEGF, ADCY7, and ADCY9) in cerebral aneurysm tissue that are associated with the estrogen receptor pathway. Further analysis of estrogen-associated differentially expressed genes may provide information about the protective effects of estrogen on cerebral aneurysm development.