Abstract：
Currently, there are no effective methods for predicting the rupture of asymptomatic small intracranial aneurysms (IA) (<7 mm). In this study the aim was to identify early warning biomarkers in peripheral plasma for predicting IA rupture. Four experimental groups were included: ruptured intracranial aneurysm (RIA), unruptured intracranial aneurysm (UIA), traumatic subarachnoid hemorrhage control (tSAHC), and healthy control (HC) groups. Plasma proteomics of these four groups were detected using iTRAQ combined LC-MS/MS. Differentially expressed proteins (DEPs) were identified in RIA, UIA, tSAHC compared with HC. Target proteins associated with aneurysm rupture were obtained by comparing the DEPs of the RIA and UIA groups after filtering out the DEPs of the tSAHC group. The plasma concentrations of target proteins were validated using enzyme-linked immunosorbent assay (ELISA). The iTRAQ analysis showed a significant increase in plasma GPC1 concentration in the RIA group compared to the UIA group, which was further validated among the IA patients. Logistic regression analysis identified GPC1 as an independent risk factor for predicting aneurysm rupture. The ROC curve indicated that the GPC1 plasma cut-off value for predicting aneurysms rupture was 4.99 ng/ml. GPC1 may be an early warning biomarker for predicting the rupture of small intracranial aneurysms. SIGNIFICANCE: The current management approach for asymptomatic small intracranial aneurysms (<7 mm) is limited to conservative observation and surgical intervention. However, the decision-making process regarding these options poses a dilemma due to weighing their respective advantages and disadvantages. Currently, there is a lack of effective diagnostic methods to predict the rupture of small aneurysms. Therefore, our aim is to identify early warning biomarkers in peripheral plasma that can serve as quantitative detection markers for predicting intracranial aneurysm rupture. In this study, four experimental populations were established: small ruptured intracranial aneurysm (sRIA) group, small unruptured intracranial aneurysm (sUIA) group, traumatic subarachnoid hemorrhage control (tSAHC) group, and healthy control (HC) group. The tSAH group was the control group of spontaneous subarachnoid hemorrhage caused by ruptured aneurysm. Compared with patients with UIA, aneurysm tissue and plasma GPC1 in patients with RIA is significantly higher, and GPC1 may be an early warning biomarker for predicting the rupture of intracranial small aneurysms.
摘要：
目前,目前尚无有效的方法来预测无症状的颅内小动脉瘤(IA)(<7mm)的破裂。在这项研究中，目的是确定外周血浆中的早期预警生物标志物，以预测IA破裂。包括四个实验组：颅内动脉瘤破裂（RIA），未破裂颅内动脉瘤（UIA），创伤性蛛网膜下腔出血控制（tSAHC），健康对照组（HC）。使用iTRAQ联合LC-MS/MS检测这四组的血浆蛋白质组学。在RIA中鉴定了差异表达蛋白（DEP），UIA,TSAHC与HC相比。在滤出tSAHC组的DEP后,通过比较RIA和UIA组的DEP获得与动脉瘤破裂相关的靶蛋白。使用酶联免疫吸附测定(ELISA)验证靶蛋白的血浆浓度。iTRAQ分析显示，与UIA组相比，RIA组血浆GPC1浓度显著增加，这在IA患者中得到了进一步验证。Logistic回归分析确定GPC1是预测动脉瘤破裂的独立危险因素。ROC曲线显示预测动脉瘤破裂的GPC1血浆临界值为4.99ng/ml。GPC1可能是预测颅内小动脉瘤破裂的早期预警生物标志物。意义：目前无症状颅内小动脉瘤（<7mm）的治疗方法仅限于保守观察和手术干预。然而,由于权衡各自的优缺点，有关这些选择的决策过程陷入了两难境地。目前,目前缺乏预测小动脉瘤破裂的有效诊断方法。因此,我们的目的是确定外周血浆中的早期预警生物标志物,这些标志物可作为预测颅内动脉瘤破裂的定量检测标志物.在这项研究中,建立了四个实验群体:颅内小破裂动脉瘤(sRIA)组,颅内小动脉瘤未破裂(sUIA)组,创伤性蛛网膜下腔出血控制（tSAHC）组，健康对照组(HC)。tSAH组为动脉瘤破裂所致自发性蛛网膜下腔出血的对照组。与UIA患者相比，RIA患者的动脉瘤组织和血浆GPC1明显增高，GPC1可能是预测颅内小动脉瘤破裂的早期预警生物标志物。
