Serum proteomics reveals the proteomic characteristics involved in the progressive feature of acute ischemic stroke (AIS)

Background To distinguish acute progressive ischemic stroke (APIS) from acute non-progressive ischemic stroke (ANPIS) is clinically critical for the precise treatment and prevention of acute ischemic stroke (AIS) deterioration. Serum proteins could reflect the unique pathophysiological processes of APIS. It is expected to find serum protein biomarkers to identify APIS at the early state, especially when typical symptoms have not been present in conventional clinical indices. Methods We recruited 178 subjects, including 133 AIS patients and 45 healthy controls. The discovery set, which included 10 age- and sex- matched cases from each of the APIS, ANPIS and control groups, was used for serum proteomic analysis with a mass spectrometry-based proteomics. The disrupted proteins of APIS were screened, of which, those common to ANPIS and specific to APIS were particularly concerned. Potential biomarkers of APIS were screened based on the theoretical knowledge to explain the mechanism and diagnostic value, and subsequently tested in the validated set (25 APIS patients, 88 ANPIS patients, and 35 controls). Results We found that 46 serum proteins were disturbed in the APIS patients; 23 differentially expressed proteins (DEPs) were common to these two groups, and 23 DEPs were associated with APIS alone. Enrichment analysis suggested that complement activation, cytolysis, proteolysis, positive regulation of fibrinolysis, blood coagulation were specifically associated with APIS; while inflammatory response, neutrophil chemotaxis, oxygen transport, and positive regulation of cell death process were common to AIPS and ANPIS. Serum amyloid A1 (SAA1) and S100 calcium binding protein A9 (S100-A9) jointly conferred a moderate value (AUC = 0.799) to diagnose APIS and to distinguish APIS from ANPIS (AUC = 0.699). Conclusions This study provides human serum proteomic evidence that inflammation, oxidative stress, and necrosis in APIS are common to ANPIS; the progressive feature of APIS may be mainly associated with complement activation, more serious inflammation, and lipid metabolic disorder; SAA1 and S100-A9 may be considered as potential biomarker panel of APIS.