Wang Chenchen, Han Yuwei, Huo Da, Li Xiaoming, Liang Guobiao
Institute of Neurology, General Hospital of Northern Theater Command, Shenyang, 110016, Liaoning, China.
J Mol Neurosci. 2025 Mar 13;75(1):33. doi: 10.1007/s12031-024-02305-4.
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.
随着神经影像学技术的进步，未破裂颅内动脉瘤（UIA）的检出率逐渐提高。然而，目前尚无有效的方法来评估和预测小型颅内动脉瘤（sIA，直径<7mm）的破裂风险。我们之前通过iTRAQ联合LC-MS/MS蛋白质定量技术，将细胞外基质蛋白2（ECM2）鉴定为预测颅内动脉瘤（IA）破裂的潜在候选生物标志物，因此本研究旨在进一步验证血浆ECM2表达水平预测IA破裂的能力。这项前瞻性、观察性、单中心队列研究纳入了322例颅内动脉瘤破裂（RIA，N = 123）、UIA（N = 89）、创伤性蛛网膜下腔出血（tSAH，N = 55）或健康对照（HC，N = 55）的个体。使用酶联免疫吸附测定（ELISA）对血浆ECM2水平进行定量。采用Spearman等级相关分析来检验变量之间的关系。使用逻辑回归分析确定sIA破裂的独立危险因素。ROC曲线评估sIA破裂的预测能力。RIA患者的血浆ECM2明显高于UIA、tSAH和HC组。无症状UIA组、HC组和tSAH组之间的血浆ECM2水平无显著差异。有症状UIA患者与RIA患者之间的血浆ECM2水平也无显著差异。此外，sIA患者的血浆ECM2水平与高血压病史密切相关。血浆ECM2水平是sIA破裂的独立危险因素。预测IA破裂的血浆ECM2临界值确定为1540.67 pg/ml。ECM2水平与动脉瘤位置的联合提高了预测准确性（AUC = 0.828，敏感性87.0%，特异性68.8%，准确性83.2%），超过了PHASES和ELPASS评分的表现。ECM2可能作为预测sIA破裂的早期预警生物标志物。
