Lipidomic profiling identifies key pathways and a 5-lipid panel with high diagnostic efficacy for ischemic stroke

Area of Science:

• Biochemistry
• Metabolomics
• Genomics

Background:

• Ischemic stroke (IS) is a leading cause of disability with limited treatments.
• Dysregulated lipid metabolism is implicated in IS pathogenesis.
• Early diagnostic biomarkers are crucial for IS management.

Purpose of the Study:

• To investigate lipid metabolism pathways altered in IS.
• To identify and validate plasma lipid biomarkers for IS diagnosis.

Main Methods:

• Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets using Gene Set Enrichment Analysis (GSEA).
• Case-control study employing Chi-square/Z tests, Liquid Chromatography-Mass Spectrometry (LC-MS), and Receiver Operating Characteristic (ROC) curve analysis.
• Validation of differentially expressed lipids in an independent cohort.

Main Results:

• Five lipid metabolism pathways (α-linolenic acid, linolenic acid, ether lipid, glycerophospholipid, sphingolipid) were significantly downregulated in IS.
• IS patients showed characteristic dyslipidemia (elevated TC, TG, LDL-C; reduced HDL-C).
• Fifteen differentially expressed lipid molecules were identified, with five showing high diagnostic potential (AUC=0.917).

Conclusions:

• Altered lipid metabolism is a key feature of ischemic stroke.
• Specific plasma lipids, such as PE(P-18:1/22:4), show promise as early diagnostic biomarkers for IS.
• These findings contribute to understanding IS pathogenesis and developing novel diagnostic strategies.