Proteomic profiling identifies novel inflammation-related plasma proteins associated with ischemic stroke outcome

Abstract

Background The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses. Methods Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects. Results Twenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke. Conclusions We identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-κB. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome.

Serum Olink Proteomics-Based Identification of Protein Biomarkers Associated with the Immune Response in Ischemic Stroke

“…In addition, we constructed and verified an IS diagnostic model consisting of six biomarkers, i.e., the abovementioned four proteins and two other immune response-related proteins: MASP1, CLEC4D, PIK3AP1, STC1, PTH1R, and HCLS1. The model demonstrated comparable or superior accuracy to IS models utilizing routine clinical hematology and biochemical characteristics, 43 inflammation-associated proteins, 44 or noncoding RNAs 45 in the bloodstream. However, it is important to note that our study focused solely on elucidating protein alterations at the immune level.…”

Differential expression of plasma proteins in pregnant women exposed toPlasmodium falciparummalaria

“…PEA technology enables simultaneous measurement of a large number of proteins using minute amount of sample [7,10]. Studies using this approach have demonstrated its clinical utility in identifying important biomarkers for various diseases, including cancer, long COVID, ischemic stroke, and early pregnancy bleeding [10][11][12][13][14][15]. In this study, we used PEA to screen sera from pregnant, malaria-exposed women to identify differentially expressed proteins.…”