Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatase 1: A Meaningful and Independent Marker to Predict Stroke in the Chinese Population

Abstract

Label-free liquid chromatography-mass spectrometry (LC-MS) quantification methods have been described to determine serum proteins biomarkers in many diseases. Thus, the purpose of this study was to investigate the serum proteins biomarkers 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. Immunoaffinity subtraction was used to deplete the top most abundant serum proteins; the remaining serum proteins were subjected to trypsin digestion and analyzed in triplicate by label-free LC-MS/MS. 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 curve (ROC). 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 Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (SHIP-1) with stroke (P < 0.001) was confirmed using ELISA in replication studies. Based on the ROC curve, the optimal cut-off value of serum SHIP-1 levels for diagnosis of stroke was projected to be 1,550 pg/ml, which yielded a sensitivity of 77.5% and a specificity of 88.3%. In multivariate analysis, there was an increased risk of AIS associated with SHIP-1 levels ≥ 1,550 pg/ml (OR 4.28, 95% CI: 1.97-8.96) after adjusting for possible confounders. The discovery and replication studies presented here show SHIP-1 to be a risk marker for AIS in the Chinese population, which appears to be a novel finding.