ABSTRACT
Objective To screen the glycoproteins as biomarkers for intracranial aneurysm (ⅠA) in cerebrospinal fluid (CSF) and evaluate the specificity and sensitivity of the biomarker candidates.Methods A complementary proteomic approach integrated with multidimensional chromatography was employed to simultaneously measure relative changes in the gylcoproteins of cerebrospinal fluid (CSF) obtained from patients with ruptured ⅠA (RIA) and unruptured ⅠA (UIA) compared to the healthy controls (HC) and disease controls (DC).One protein-receptor tyrosine kinase Axl with a unique change in RIA was validated in CSF and plasma.The sensitivity at 95％ specificity of Axl in CSF and plasma was evaluated with receiver operating characteristic curve (ROC curve).Results Firstly,a total of 294 glycoproteins were identified in human CSF with believable evidence.Secondly,the proteomic findings showed the quantitative changes in RIA and UIA as compared to HC and DC.Of 294 identified CSF proteins,59,24 and 33 proteins displayed quantitative changes unique to RIA,UIA or IA,respectively.At last,one of these unique proteins-receptor tyrosine kinase Axl with unique increase in RIA was confirmed both in CSF and plasma.ROC curve analysis showed that the sensitivity at 95％ specificity of Axl in CSF to differentiate RIA from UIA was 60％.When compared to CSF,the sensitivity at above setting in plasma to differentiate RIA from HC was 40％ and to differentiate RIA from UIA was 25％.Conclusions A glycoprotein biomarker Axl might be used as a promising biomarker to predict the rupture of ⅠA.The further investigation of the relations between Axl and IA formation as well as rupture might help to elucidate the underlying pathogenesis and find new therapeutic targets.