Plasma Extracellular Matrix Protein 2 Level as a Predictive Biomarker for Rupture of Small Intracranial Aneurysms

As the neuroimaging technology improves, the detection rate of unruptured intracranial aneurysms (UIA) is gradually increasing. However, there is currently no effective means to evaluate and predict the risk of rupture for small intracranial aneurysm (sIA, diameter < 7 mm). We previously identified extracellular matrix protein 2 (ECM2) as a potential candidate biomarker for predicting intracranial aneurysm (IA) rupture through iTRAQ combined with LC-MS/MS protein quantification technology, so this study aimed to further validate the ability of plasma ECM2 expression levels to predict IA rupture. This prospective, observational, single-center cohort study enrolled 322 individuals with ruptured intracranial aneurysm (RIA, N = 123), UIA (N = 89), traumatic subarachnoid hemorrhage (tSAH, N = 55), or healthy controls (HC, N = 55). ECM2 plasma levels were quantified using enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation analysis was employed to examine the relationship between variables. Independent risk factors of sIA rupture were identified using logistic regression analysis. The ROC curve assessed the predictive capability for sIA rupture. Plasma ECM2 was notably higher in RIA patients than in UIA, tSAH, and HC groups. Plasma ECM2 levels showed no significant difference among the asymptomatic UIA, HC, and tSAH groups. There was also no significant difference in plasma ECM2 levels between symptomatic UIA patients and RIA patients. Furthermore, the plasma ECM2 level was closely related to hypertension history in sIA patients. ECM2 plasma level was an independent risk factor for sIA rupture. The plasma ECM2 cutoff level for predicting IA rupture was determined to be 1540.67 pg/ml. The combination of ECM2 levels and aneurysm location increased predictive accuracy (AUC = 0.828, sensitivity 87.0%, specificity 68.8%, accuracy 83.2%), surpassing the performance of PHASES and ELPASS scores. ECM2 could potentially act as an early warning biomarker for predicting the rupture of sIAs.