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

    Final Number:
    507

    Authors:
    Pui Man Rosalind Lai BA , MD; Rose Du MD, PhD

    Study Design:
    Other

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting

    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

    References: 1. Lin B, Chen W, Ruan L, et al. Sex differences in aneurysm morphologies and clinical outcomes in ruptured anterior communicating artery aneurysms: a retrospective study. BMJ Open. Apr 15 2016;6(4):e009920. 2. Harrod CG, Batjer HH, Bendok BR. Deficiencies in estrogen-mediated regulation of cerebrovascular homeostasis may contribute to an increased risk of cerebral aneurysm pathogenesis and rupture in menopausal and postmenopausal women. Med Hypotheses. 2006;66(4):736-756. 3. Stober T, Sen S, Anstatt T, Freier G, Schimrigk K. Direct evidence of hypertension and the possible role of post-menopause oestrogen deficiency in the pathogenesis of berry aneurysms. J Neurol. 1985;232(2):67-72. 4. Hamdan A, Barnes J, Mitchell P. Subarachnoid hemorrhage and the female sex: analysis of risk factors, aneurysm characteristics, and outcomes. J Neurosurg. Dec 2014;121(6):1367-1373. 5. Harrod CG, Batjer HH, Bendok BR. Deficiencies in estrogen-mediated regulation of cerebrovascular homeostasis may contribute to an increased risk of cerebral aneurysm pathogenesis and rupture in menopausal and postmenopausal women. Med Hypotheses. 2006;66(4):736-756. 6. Tada Y, Makino H, Furukawa H, et al. Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice. Neurosurgery. Dec 2014;75(6):690-695; discussion 695. 7. Crago EA, Sherwood PR, Bender C, Balzer J, Ren D, Poloyac SM. Plasma Estrogen Levels Are Associated With Severity of Injury and Outcomes After Aneurysmal Subarachnoid Hemorrhage. Biol Res Nurs. Oct 2015;17(5):558-566.

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