Introduction: Estrogen is thought to play a role in the protection against the development of cerebral aneurysms. The objective of the study is to identify differentially expressed genes in the downstream estrogen receptor pathway that may be associated with development of aneurysms.
Methods: Data from six Gene Expression Omnibus (GEO) databases with gene expression profiles of cerebral aneurysm tissue were analyzed (GSE6551, GSE15629, GSE26969, GSE46337, GSE54083, GSE75436). 94 genes associated with the estrogen receptor pathway were identified from the KEGG 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, of which two were down-regulated (PIK3R1, fold change [FC] 0.41, FDR=6.1x10-5; ADCY9, FC 0.55, FDR=2.3x10-4), and two were up-regulated (HBEGF FC 1.46, FDR=4.9x10-4; ADCY7 FC 2.11, FDR=6.0x10-3). 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=6.3x10-5) and women (FC 0.46, FDR=2.3x10-4).
Conclusions: The analysis of 6 GEO databases revealed four differential expressed genes (PIK3R1, HBEGF, ADCY7, 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 estrogens and its underlying mechanism on cerebral aneurysm development.
Patient Care: While there are animal models that demonstrate estrogen’s protective role in the development of cerebral aneurysms, the downstream estrogen receptor pathway remains to be elucidated. The identification of genes in the pathway may provide a better understanding of the mechanism of disease and identify diagnostic and therapeutic targets.
Learning Objectives: By the conclusion of this session, participants should be able to:
1) Understand the estrogen pathway plays a role in the protection against the development of aneurysms
2) Identify downstream genes which may be associated with cerebral aneurysm development
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