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

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).

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.

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.

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.