Identification of autophagy-related biomarkers in the circulatory system of ischemic stroke.

Objectives: Increasing evidence indicates autophagy's dual role in ischemic stroke (IS), though its mechanisms and biomarkers remain unclear. This study analyzes autophagy-related genes (ARGs) and constructs a circRNA-miRNA-mRNA network to identify key ARGs and their interactions.

Materials and methods: Differentially expressed genes from GEO were intersected with HADb-derived autophagy-related genes (ARGs) to identify DEARGs. Target mRNAs of DEmiRNAs and DEcircRNAs were predicted via mirDIP and circBank, respectively, and integrated to construct a circRNA-miRNA-mRNA regulatory network. Key genes were screened through PPI analysis, followed by immune infiltration analysis and experimental validation.

Results: In IS, 539 circRNAs, 61 miRNAs, and 565 mRNAs were identified with differential expression. A circRNA-miRNA-autophagy related mRNA network was established, identifying multiple regulatory relationship pairs. Notably, five autophagy-related hub genes demonstrated significant correlations with immune cell infiltration. Clinical validation further confirmed that (HIF1A) and (EIF2AK2) were significantly upregulated, while (HSPA8) was significantly downregulated, underscoring their potential relevance in IS.

Conclusion: HIF1A, EIF2AK2, and HSPA8 May serve as biomarkers for early diagnosis of IS. This study reveals fresh insights into the molecular mechanisms linked to IS.