The scientific basis of
intracranial aneurysm (IA) formation, its
rupture and further development of
cerebral vasospasm is incompletely understood. Aberrant
protein expression may drive structural alterations of vasculature found in IA. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection
biomarkers and in turn, improved treatment outcomes. To unravel differential
protein expression in three clinical subgroups of IA patients: (1) unruptured
aneurysm, (2)
ruptured aneurysm without vasospasm, (3)
ruptured aneurysm who developed vasospasm, we performed untargeted quantitative proteomic analysis of
aneurysm tissue and serum samples from three subgroups of IA patients and control subjects. Candidate molecules were then validated in a larger cohort of patients using
enzyme-linked
immunosorbent assay. A total of 937 and 294
proteins were identified from
aneurysm tissue and serum samples, respectively. Several
proteins that are known to maintain structural integrity of vasculature were found to be dysregulated in the context of
aneurysm. ORM1, a
glycoprotein, was significantly upregulated in both tissue and serum samples of unruptured
aneurysm patients. We employed a larger cohort of subjects (n = 26) and validated ORM1 as a potential
biomarker for screening of unruptured
aneurysms. Samples from
ruptured aneurysms with vasospasm showed significant upregulation of MMP9, a
protease, compared with
ruptured aneurysms without vasospasm. We validated MMP9 as a potential
biomarker for vasospasm in a larger cohort (n = 52). This study reports the first global proteomic analysis of the entire clinical spectrum of IA. Furthermore, this study suggests ORM1 and MMP9 as potential
biomarkers for unruptured
aneurysm and
cerebral vasospasm, respectively.