Glypican-1 may be a plasma biomarker for predicting the rupture of small intracranial aneurysms.

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. SignificanceThe 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.