Serum protein biomarkers screening in patients with ischemic stroke by LC-MS/MS.

Background: The purpose of this study was to investigate the serum proteins biomarkers by label-free liquid chromatography coupled to tandem mass spectrometry quantification methods in the Chinese patients with acute ischemic stroke (AIS).

Method: In the study period, sera from 40 AIS patients and 40 normal cases were selected for screening study. The selected protein associations with disease risk were further evaluated by enzyme-linked immunosorbent assay (ELISA) testing of the remaining stroke cases and controls. Its value for biomarkers diagnosis was appreciated through receiver operating characteristic (ROC) curve.

Results: Patients versus control levels differences were suggested for 19 proteins (nominal P < 0.05) for stroke, with three proteins having a false discovery rate <0.05. The association of mannose-binding lectin (MBL) with stroke (P < 0.001) was confirmed using ELISA in replication studies. Based on the ROC curve, the optimal serum concentration of MBL as a surrogate marker to support the diagnosis of ischemic cerebral injury was found to be 1050 ug/L, which yielded a sensitivity of 81.8% and a specificity of 80.2%, the area under the curve was 0.812 (95% CI: 0.724-0.876). In multivariate analysis, there was an increased risk of AIS associated with MBL levels ≥1050 ug/L (OR: 4.76, 95% CI: 1.59-10.12) after adjusting for possible confounders.

Conclusion: The discovery and replication studies presented here show MBL to be a risk marker for AIS in the Chinese population, which appears to be a novel finding.