Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke

BACKGROUND: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors.

METHODS: After the integration analysis of small RNA sequencing and mRNA PCR array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischemic stroke (IS) patients. Receiver operator characteristic (ROC) analysis was used to determine the performance of mRNAs and miRNAs expression.

RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. Besides, Fas gene level was significantly higher in unfavorable outcome patients when compared to favorable outcome patients. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among unfavorable outcome patients, suggesting Fas signal transporting through exosome in the circulating system.

CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expressions in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in IS patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.